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

Trial Summary

What is the purpose of this trial?

Donor site pain study comparing post-operative donor site pain and opioid consumption after use of Lidocaine, Liposomal Bupivicaine or regional nerve block for split thickness skin graft harvesting in patients with less than 20% TBSA burn wounds and less than %5 Deep partial or full thickness burn wounds.

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 data supports the effectiveness of the drug liposomal bupivacaine for skin graft pain?

Research shows that liposomal bupivacaine can provide pain relief for up to 72 hours after skin graft procedures, which is longer than traditional local anesthetics. This sustained-release effect helps manage pain more effectively at the donor site. ^{1 2 3 4 5}

Is liposomal bupivacaine generally safe for humans?

Liposomal bupivacaine is a local anesthetic that provides long-lasting pain relief and has been studied for its safety in various surgical settings. It has a favorable potency to toxicity ratio, meaning it is effective without being overly harmful, but there are concerns about potential nerve toxicity, especially when injected into nerves. ^{1 4 6 7 8}

How does liposomal bupivacaine differ from lidocaine for skin graft pain?

Liposomal bupivacaine is unique because it provides long-lasting pain relief for up to 72 hours after a single dose, unlike traditional local anesthetics like lidocaine, which have a shorter duration of action. This makes it particularly useful for managing the intense pain associated with skin graft donor sites. ^{1 2 3 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Intraoperative liposomal bupivacaine for skin graft donor site analgesia: A retrospective cohort study. [2021]

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

Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesic duration. [2022]

3. United States 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]. [2022]

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

Bupivacaine: a review. [2018]

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

Evaluation of Liposomal Bupivacaine at Split-Thickness Skin Graft Donor Sites Through a Randomized, Controlled Trial. [2022]

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

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

7. Germany 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. [2021]

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

Neurotoxicity of intraneural injection of bupivacaine liposome injectable suspension versus bupivacaine hydrochloride in a porcine model. [2019]

9. England 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. [2021]

10. Netherlands 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. [2022]