Liposomal Bupivacaine vs Lidocaine for Skin Graft Pain

Overseen By Dhaval Bhavsar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Kansas Medical Center

Disqualifiers: Chronic pain, Pregnancy, Allergies, 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: 6

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different methods to manage pain after skin graft surgery for burn patients. It compares three pain relief methods: Liposomal Bupivacaine (a long-acting local anesthetic), regular Lidocaine (a local anesthetic), and a regional nerve block (anesthesia that numbs a specific area). The goal is to determine which method best reduces pain and the need for opioid painkillers after surgery. Candidates with burn injuries covering less than 20% of their body and not too deep may be suitable for this trial. As a Phase 4 trial, this research involves treatments already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What is the safety track record for these treatments?

Research has shown that liposomal bupivacaine is generally safe for patients, providing pain relief for up to 72 hours after skin grafts, which lasts longer than regular local painkillers. This extended relief suggests it is a safe treatment option.

For bupivacaine used in nerve blocks, studies indicate it significantly reduces the need for narcotics after surgery. This is beneficial because patients experience less pain without heavily relying on other painkillers. This method of pain control is effective and usually well-received by patients.

Both treatments aim to manage pain effectively while ensuring patient safety. Evidence suggests they are well-tolerated, with few side effects reported. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for skin graft pain because they offer innovative ways to manage pain effectively. Liposomal bupivacaine is unique because it provides extended pain relief by slowly releasing the anesthetic over time, potentially reducing the need for repeated dosing compared to traditional options like lidocaine. The use of a bupivacaine nerve block for regional anesthesia targets specific nerve areas, which might enhance pain management by addressing pain directly at its source, rather than just at the surface level. These approaches could offer longer-lasting and more targeted pain relief, which is a significant advancement over current standard treatments.

What evidence suggests that this trial's treatments could be effective for skin graft pain?

In this trial, participants will receive different treatments to manage pain after skin graft surgery. Research has shown that liposomal bupivacaine, administered to participants in Group 1, can greatly reduce pain at the donor site. One study found that patients who received liposomal bupivacaine reported significantly less pain in the days following surgery compared to those who did not receive it. Another study found that it could even completely prevent pain for the first three days after surgery.

Participants in Group 3 will receive bupivacaine nerve blocks. Research indicates that bupivacaine nerve blocks can significantly improve pain levels and reduce the need for pain medication after surgery. They have also been associated with shorter hospital stays.

Participants in Group 2 will receive lidocaine, serving as an active comparator in this trial. Both liposomal bupivacaine and bupivacaine nerve blocks offer promising ways to manage pain after skin grafts. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for English or Spanish speakers with less than 20% total body surface area (TBSA) burned and less than 5% deep partial/full thickness burns. It's not for those with chronic pain conditions, more extensive burns, pregnancy, or allergies to local anesthetics like lidocaine.

Inclusion Criteria

You have less than 20% of your body surface area burned, with less than 5% of that being deep burns.

Spanish/English speaking

Exclusion Criteria

Burns on the front of the thighs.

Pregnant

You have a long-lasting pain condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Randomized controlled study with injection of lidocaine with epinephrine or liposomal bupivacaine at the donor site

1 day

1 visit (in-person)

Treatment Phase 2

All subjects receive regional anesthesia with a nerve block based on the proposed donor site location

1 day

1 visit (in-person)

Follow-up

Participants are monitored for pain levels and opioid consumption post-operatively

3 days

Pain assessments at 4, 8, 12, 24, 48, and 72 hours post-operatively

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine Hydrochloride
• Lidocaine Hydrochloride
• Liposomal bupivacaine

Trial Overview The study compares the effectiveness of Lidocaine, Liposomal Bupivacaine, and regional nerve block in managing post-operative pain at skin graft donor sites in burn patients. It also looks at how these treatments affect opioid use after surgery.

How Is the Trial Designed?

Group I: Group 3 Experimental Treatment 1 Intervention

Subjects will receive regional anesthesia with a bupivacaine nerve block; either a fascia iliaca, lateral femoral cutaneous, or femoral nerve block based on the proposed donor site location

Group II: Group 1 Experimental Treatment 1 Intervention

Liposomal Bupivicaine (266mg/20ml) will be diluted into Lactated Ringer solution (280 ml) and injected once intra-operatively subcutaneously before donor site harvesting

Group III: Group 2 Active Control 1 Intervention

Lidocaine (50 mg/50 ml) will be diluted into Lactated Ringer (1000ml) and injected once subcutaneously before donor site harvesting

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

Liposomal bupivacaine is a prolonged-release local anesthetic that can effectively manage intense donor site pain following skin graft procedures.

This treatment offers a potential solution for patients experiencing difficult-to-treat pain after surgery, improving their overall postoperative comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine for the management of postsurgical donor site pain in patients with burn injuries: a case series from two institutions. Dissanaike, S., McCauley, J., Alphonso, C.[2021]

In a study of 30 adolescent and young adult burn patients undergoing reconstructive skin graft procedures, liposomal bupivacaine infiltration significantly reduced postoperative pain scores compared to standard bupivacaine treatment, with lower scores at both 0-4 hours and 0-24 hours post-surgery.

Neither liposomal bupivacaine nor standard treatment was associated with adverse events, indicating that liposomal bupivacaine is a safe option for pain management, although the differences in pain relief may not be clinically significant, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of liposomal bupivacaine infiltration at reconstructive skin graft donor sites in adolescent and young adult burn patients: A retrospective analysis. Sadeq, F., DePamphilis, MA., Dabek, RJ., et al.[2022]

Liposomal formulations of local anesthetics (prilocaine, lidocaine, and mepivacaine) significantly enhanced the anesthetic effect and prolonged recovery time compared to plain solutions, with mepivacaine showing the greatest improvement.

The study demonstrated that liposomes are effective drug-delivery systems for local anesthetics, although lidocaine benefited the least from encapsulation, likely due to its stronger vasodilatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesic duration : [Des préparations liposomiques de prilocaïne, de lidocaïne et de mépivacaïne prolongent la durée de l'analgésie]. Saia Cereda, CM., Brunetto, GB., de Araújo Phd, DR., et al.[2022]

In a randomized controlled trial involving 50 adult burn patients, liposomal bupivacaine did not show any significant advantage over standard lidocaine for managing pain at split-thickness skin graft donor sites, with similar pain scores reported postoperatively.

There was also no difference in opioid consumption between the two groups, indicating that liposomal bupivacaine may not be a more effective option for pain management in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Liposomal Bupivacaine at Split-Thickness Skin Graft Donor Sites Through a Randomized, Controlled Trial. Egan, KG., Guest, R., Sinik, LM., et al.[2022]

In a study of 58 patients undergoing skin graft procedures, those who received liposomal bupivacaine reported significantly lower donor site pain on postoperative days 0 and 1, with 86% rating their pain as three or less, compared to only 3.4% in the control group.

Liposomal bupivacaine not only reduced pain levels but also made the donor site less bothersome for patients, with 76% stating it was less painful than the graft site, indicating its potential as a safe and effective option for prolonged postoperative analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative liposomal bupivacaine for skin graft donor site analgesia: A retrospective cohort study. Artz, C., Ward, MA., Miles, MVP., et al.[2021]

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 study of 20 patients undergoing lingual nerve microsurgery, those who received liposomal bupivacaine (LB) reported significantly less postoperative pain and consumed fewer opioid pills compared to those who received bupivacaine hydrochloride (BH).

The findings suggest that LB, with its prolonged duration of action, is more effective in reducing postoperative pain and opioid consumption, supporting its use in surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine use in exploratory lingual nerve microsurgery: does liposomal bupivacaine use decrease postoperative pain and opioid consumption compared to bupivacaine hydrochloride? A pilot study. Jacobus, D., Mehr, S., Ziccardi, V.[2021]

Liposomal formulations of local anesthetics (prilocaine, lidocaine, and mepivacaine) significantly enhanced their anesthetic effects and prolonged recovery times compared to plain solutions, with mepivacaine showing the greatest improvement.

The study demonstrated that liposomes can serve as effective drug-delivery systems for local anesthetics, suggesting potential for better pain management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesic duration. Cereda, CM., Brunetto, GB., de Araújo, DR., et al.[2022]

Bupivacaine hydrochloride (Marcaine) is highlighted for its increased duration of action compared to other local anesthetics, making it particularly useful in oral surgery.

It also has a favorable potency to toxicity ratio, suggesting that it provides effective pain relief with a lower risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine: a review. Babst, CR., Gilling, BN.[2018]

Bupivacaine liposome injectable suspension provided significantly longer sensory (11.2 hours) and motor (10.0 hours) blockade compared to standard bupivacaine HCl (3.2 hours sensory and 4.0 hours motor), indicating enhanced efficacy in pain management.

Both formulations of bupivacaine, when injected intraneurally in pigs, showed no signs of neurotoxicity, as there were no changes in axonal density or myelin structure, suggesting they are safe for use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotoxicity of intraneural injection of bupivacaine liposome injectable suspension versus bupivacaine hydrochloride in a porcine model. Damjanovska, M., Cvetko, E., Kuroda, MM., et al.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0305417925002876

Bupivacaine hydrochloride-soaked dressings versus ... This study aimed to compare the efficacy of bupivacaine hydrochloride-soaked dressings with subcutaneous infiltration for managing postoperative donor site pain ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7644829/

Regional Anesthetic Blocks for Donor Site Pain in Burn ... Regional nerve blocks have been shown to improve pain scores, decrease narcotic consumption, and shorten hospital stays in the orthopedic literature. The ...

3. journals.lww.com journals.lww.com/ijob/fulltext/2020/28010/a_prospective_study_on_efficacy_of_topical.5.aspx

A prospective study on efficacy of topical bupivacaine in... The objective of this study was to compare the effectiveness of bupivacaine-soaked gauze dressing and conventional dressing for pain relief in patients ...

4. researchgate.net researchgate.net/publication/351796938_A_prospective_study_on_efficacy_of_topical_bupivacaine_in_split_skin_grafting_donor_site_in_immediate_postoperative_pain_relief

A prospective study on efficacy of topical bupivacaine in ... Objective: The objective of this study was to compare the effectiveness of bupivacaine-soaked gauze dressing and conventional dressing for ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9486980/

Systematic literature review of topical local anaesthesia or ... Topical local anaesthetics (lidocaine or bupivacaine) provide good analgesia, both during and after STSG harvest, at well below toxic serum levels.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03854344

Liposomal Bupivacaine Versus Lidocaine for Skin Graft ... Donor site pain study comparing post-operative donor site pain and opioid consumption after use of Lidocaine, Liposomal Bupivicaine or regional nerve block for ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ccr3.1292

Liposomal bupivacaine for the management of postsurgical ... Infiltration of liposomal bupivacaine into the graft donor sites in burn-injured patients undergoing skin grafting was well tolerated and ...