Pain Relief Methods for Breast Cancer Surgery

Overseen By Grant A Miller, DO

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: United States Naval Medical Center, Portsmouth

Must not be taking: Antithrombotics

Disqualifiers: Allergy, Infection, Neural deficits, Coagulopathy, 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: 1

Duration: Immediate pre-surgery

200 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 mentions that patients taking antithrombotic drugs outside certain guidelines are excluded. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug for pain relief in breast cancer surgery?

Research shows that liposomal bupivacaine (Exparel) can effectively reduce pain and shorten hospital stays after breast surgery, while dexmedetomidine helps reduce chronic pain after breast cancer surgery. ^{1 2 3 4 5}

Is liposomal bupivacaine (Exparel) safe for use in humans?

Liposomal bupivacaine (Exparel) has been shown to be a safe pain reliever in various surgical settings, including breast reconstruction, with studies indicating it can reduce pain and hospital stay without significant complications. However, it is not approved for use in certain areas like the neuraxial space, and its safety in these areas is still being studied. ^{1 3 5 6 7}

How does the drug liposomal bupivacaine differ from other pain relief options for breast cancer surgery?

Liposomal bupivacaine is unique because it is a slow-release form of bupivacaine that can provide extended pain relief for several days after surgery, potentially reducing the need for opioids and shortening hospital stays. ^{1 2 3 8 9}

What is the purpose of this trial?

Perform a comparison of effective pain relief duration between liposomal bupivacaine and dexmedetomidine when added to bupivacaine in a block for mastectomy for cancer surgery. The erector spinae plane block is a well-established block that is utilized for post operative pain control for procedures performed on the soft tissue of the chest and chest wall as well as intrathoracic procedures. The goal is comparison of the effective duration of both study groups to determine if there is a significant difference in time and amount of post operative opioids required which admitted to hospital.

Eligibility Criteria

This trial is for patients undergoing any type of mastectomy, with or without axillary lymph node dissection. Participants must consent to a peripheral nerve block and agree to be part of the study. The anesthesia team must approve the block based on medical history, and the surgeon must agree with the plan.

Inclusion Criteria

I need a mastectomy, possibly with lymph node removal.

I agree to participate in the study.

I agree to have a peripheral nerve block.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an erector spinae plane block with either liposomal bupivacaine or bupivacaine with dexmedetomidine for postoperative pain control during mastectomy surgery

Immediate pre-surgery

1 visit (in-person)

Postoperative Monitoring

Participants' pain scores and morphine equivalence are monitored every 6 hours while inpatient, and pain scores are collected up to 72 hours post-discharge

96 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexmedetomidine
• Liposomal Bupivacaine

Trial Overview The study compares two pain relief methods in post-mastectomy care: liposomal bupivacaine versus bupivacaine mixed with dexmedetomidine in an erector spinae plane block. It aims to determine which combination provides longer-lasting pain control and reduces opioid use while hospitalized.

Participant Groups

Group I: Bupivacaine plain with dexmedetomidine Experimental Treatment 1 Intervention

Erector spinae plane block performed on the surgical side (left, right or bilateral) as appropriate based on planned surgical consent. Utilizing ultrasound to see the fascial layers and guide the needle placement under direct visualization. Block will include 0.25% bupivacaine plain 30 ml plus dexmedetomidine 0.5 mcg/kg per side of the block.

Group II: Liposomal bupivacaine and bupivacaine plain erector spinae plane block Active Control 1 Intervention

Erector spinae plane block performed on the surgical side (left, right or bilateral) as appropriate based on planned surgical consent. Utilizing ultrasound to see the fascial layers and guide the needle placement under direct visualization. Block will include 1.33% liposomal bupivacaine 10ml plus 0.25% bupivacaine plain 20 ml per side of the block.

Who Is Running the Clinical Trial?

United States Naval Medical Center, Portsmouth

Lead Sponsor

Trials

35

Recruited

4,900+

Findings from Research

Liposomal bupivacaine significantly reduced postoperative pain and the need for antiemetics in certain obesity classes, particularly showing lower pain scores immediately after surgery and at discharge for obesity class I patients.

Patients receiving liposomal bupivacaine had shorter hospital stays, especially among premenopausal women, indicating potential benefits in recovery time and overall patient outcomes compared to standard bupivacaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine May Benefit Select Reduction Mammaplasty Patients. Kalaria, SS., Boukovalas, S., Padilla, PL., et al.[2019]

In a study of 86 breast cancer surgery patients, perioperative administration of dexmedetomidine significantly reduced the incidence and severity of chronic pain compared to a saline control, as measured by standardized pain questionnaires three months post-surgery.

Patients receiving dexmedetomidine also reported better quality of life scores, indicating that this medication not only helps manage pain but also enhances overall well-being after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the perioperative infusion of dexmedetomidine on chronic pain after breast surgery. Jain, G., Bansal, P., Ahmad, B., et al.[2022]

In a study of 90 patients undergoing immediate breast reconstruction, the use of liposomal bupivacaine (LB) significantly reduced postoperative pain scores compared to traditional pain management methods, indicating its efficacy as a pain reliever.

Patients receiving LB also had a shorter hospital stay (1.5 days) compared to those on narcotics (2.0 days), with no reported adverse events, highlighting its safety and potential benefits in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Pain and Length of Stay Lowered by Use of Exparel in Immediate, Implant-Based Breast Reconstruction. Butz, DR., Shenaq, DS., Rundell, VL., et al.[2022]

In a study of 45 female patients undergoing major breast cancer surgery, the addition of dexmedetomidine to bupivacaine in paravertebral blocks significantly reduced postoperative pain and opioid consumption, leading to better overall patient satisfaction.

Patients receiving the dexmedetomidine combination experienced lower pain scores and a reduced incidence of nausea and vomiting, while maintaining similar rates of hypotension and bradycardia compared to other groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of dexmedetomidine as an adjuvant in paravertebral block in breast cancer surgery. Mohta, M., Kalra, B., Sethi, AK., et al.[2022]

In a study involving 98 mice, liposomal bupivacaine (Exparel®) provided a longer duration of pain relief compared to standard bupivacaine, with motor block lasting up to 180 minutes and thermoalgesic block lasting up to 420 minutes.

The addition of dexamethasone, either perineurally or systemically, significantly reduced neural inflammation caused by bupivacaine, and perineural dexamethasone also helped reduce inflammation from Exparel®, suggesting a protective effect against nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. Ferré, F., Krin, A., Sanchez, M., et al.[2020]

In a pilot study involving 25 pigs, subarachnoid administration of liposomal bupivacaine resulted in a longer duration of pain relief compared to standard bupivacaine hydrochloride, with effects lasting up to 32 hours for higher doses.

No signs of neurotoxicity were observed in any treatment group, suggesting that liposomal bupivacaine may be a safe option for extended analgesia in the neuraxial space, warranting further studies for potential human use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. Zel, J., Hadzic, A., Cvetko, E., et al.[2019]

In a retrospective analysis of 575 subjects across 6 clinical trials, liposome bupivacaine showed a similar safety profile to both bupivacaine HCl and normal saline, with 76% of liposome bupivacaine recipients experiencing adverse events (AEs).

The most common AEs for liposome bupivacaine included nausea and hypesthesia, and serious AEs occurred in 8% of subjects, indicating that the side effects are likely related to the surgical procedure rather than the medication itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. Ilfeld, BM., Viscusi, ER., Hadzic, A., et al.[2022]

The case study discusses a 35-year-old woman undergoing surgery for a painful breast tumor and highlights strategies to minimize the risk of developing chronic pain after the operation.

Various methods such as preoperative medications, nerve blocks, local anesthetics, and postoperative epidural pharmacotherapy are suggested to effectively manage pain and reduce the likelihood of chronic pain post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain management discussion forum: prevention of chronic postoperative pain. Breivik, H.[2014]

In a study involving 100 patients with pulpal necrosis, liposomal bupivacaine did not show a statistically significant improvement in postoperative pain relief compared to standard bupivacaine, with success rates of 29% and 22% respectively.

While liposomal bupivacaine had some effects on soft tissue numbness and non-narcotic medication use, these effects were not clinically significant, indicating that it may not provide additional benefits over traditional bupivacaine for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Liposomal Bupivacaine (Exparel) Significantly Reduce Postoperative Pain/Numbness in Symptomatic Teeth with a Diagnosis of Necrosis? A Prospective, Randomized, Double-blind Trial. Glenn, B., Drum, M., Reader, A., et al.[2017]

References

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

Liposomal Bupivacaine May Benefit Select Reduction Mammaplasty Patients. [2019]

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

Effect of the perioperative infusion of dexmedetomidine on chronic pain after breast surgery. [2022]

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

Postoperative Pain and Length of Stay Lowered by Use of Exparel in Immediate, Implant-Based Breast Reconstruction. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Efficacy of dexmedetomidine as an adjuvant in paravertebral block in breast cancer surgery. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Pain management discussion forum: prevention of chronic postoperative pain. [2014]

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

Does Liposomal Bupivacaine (Exparel) Significantly Reduce Postoperative Pain/Numbness in Symptomatic Teeth with a Diagnosis of Necrosis? A Prospective, Randomized, Double-blind Trial. [2017]