Pain Management After VATS for Postoperative Pain

Overseen By Yatish Ranganath, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nada Sadek

Disqualifiers: Chronic pain, Opioid tolerance, Hepatic disease, 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 post-operative period

176 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have chronic pain or are opioid-tolerant, you may not be eligible to participate.

What data supports the effectiveness of the drug for managing postoperative pain?

The research indicates that liposomal bupivacaine, a form of bupivacaine that releases the drug slowly over time, does not consistently show better pain control compared to standard bupivacaine in most studies. Only a small percentage of trials found it to be more effective, and it often performed worse when compared to standard bupivacaine used in nerve blocks. ^{1 2 3 4 5}

Is liposomal bupivacaine safe for humans?

Liposomal bupivacaine (Exparel) has been approved by the FDA for use in surgical pain relief and has been shown to be safe in various settings, including breast augmentation and peripheral nerve blocks. However, it is not approved for use in certain areas like the neuraxial space, and some studies have noted potential nerve inflammation, which can be managed with additional medications like dexamethasone. ^{3 5 6 7 8}

How does liposomal bupivacaine differ from other drugs for managing postoperative pain after VATS?

Liposomal bupivacaine is unique because it is a long-acting formulation that releases the drug over 72 hours, providing extended pain relief compared to traditional bupivacaine. It is used in intercostal nerve blocks, which can offer superior pain control compared to epidural catheters, especially in the first few days after surgery. ^{4 5 9 10 11}

What is the purpose of this trial?

Video-assisted thoracoscopic surgery (VATS) greatly decreased the number and types of surgery that required open thoracotomy. Initially it was thought that VATS would lead to a reduction of respiratory problems and less acute pain in patients when compared to patients receiving an open thoracic surgery. However, for reasons not clearly understood, a large number of patients who undergo VATS still experience moderate to severe post-surgical pain. Physicians are still faced with the challenge of providing care that will manage both the respiratory issues as well as manage acute pain. The goal of this study is to find the most suitable regimen to effectively manage post-VATS-related pain.

Research Team

Nada Sadek, MD

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for adults aged 18-80 undergoing VATS who are not pregnant, have a BMI under 40, and can consent. It excludes those with chronic pain conditions, opioid tolerance, allergies to study drugs, infectious diseases, coagulation issues, severe liver disease or incarceration.

Inclusion Criteria

I am scheduled for a minimally invasive chest surgery.

You weigh less than 40 times your height in kilograms.

Exclusion Criteria

I have severe liver disease.

My blood does not clot properly.

I have had a surgery to fuse my lung lining using a camera-assisted technique.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either an intercostal nerve block with liposomal bupivacaine or a paravertebral block with plain bupivacaine

Immediate post-operative period

1 visit (in-person)

Post-operative Monitoring

Participants are monitored for post-operative pain, opioid usage, and lung function

Up to 72 hours post procedure

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain scores and opioid consumption

Up to 6 months post procedure

Treatment Details

Interventions

• Bupivacaine
• Liposomal bupivacaine

Trial Overview The study tests two types of pain management medications after VATS: Bupivacaine and Liposomal bupivacaine. The aim is to determine which provides better post-surgical pain relief without causing respiratory problems.

Participant Groups

Group I: Liposomal bupivacaine Experimental Treatment 1 Intervention

The patient will receive an intercostal nerve block by the surgeon in the operating room after anesthetic has been administered. The surgeon will use thoracoscopic guidance to administer the intercostal nerve block. The medication used in this block will liposomal bupivacaine (Exparel).

Group II: Bupivacaine Active Control 1 Intervention

The patient will receive a paravertebral block by the anesthesiologist staffing the pain service area within the hospital prior to surgery. This regional anesthesia will be done using ultrasound guidance. The medication used in this block will be plain bupivacaine with epinephrine.

Who Is Running the Clinical Trial?

Nada Sadek

Lead Sponsor

Trials

1

Recruited

180+

YATISH SIDDAPURA RANGANATH

Lead Sponsor

Trials

2

Recruited

300+

Rakesh Sondekoppam Vijayashankar

Lead Sponsor

Trials

2

Recruited

320+

American Society of Regional Anesthesia

Collaborator

Trials

5

Recruited

310+

Findings from Research

A review of 76 randomized controlled trials found that only 11% showed a significant benefit of liposomal bupivacaine over standard bupivacaine or ropivacaine for postoperative pain control.

The majority of trials indicated that unencapsulated bupivacaine provided better pain relief than liposomal bupivacaine, suggesting that routine use of liposomal bupivacaine may not be justified based on current evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Ilfeld, BM., Eisenach, JC., Gabriel, RA.[2021]

In a randomized controlled trial involving 57 patients undergoing midurethral sling placement, liposomal bupivacaine resulted in lower median pain scores on postoperative day 1 compared to a mixture of bupivacaine and lidocaine (20 mm vs 30 mm), indicating some efficacy in pain management.

Despite the initial lower pain scores, there were no significant differences in overall opioid and nonsteroidal anti-inflammatory drug consumption or in quality of recovery scores after 7 days, suggesting that liposomal bupivacaine may not provide a clinically significant advantage over traditional pain management methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Bupivacaine Hydrochloride with Lidocaine during Midurethral Sling Placement: A Randomized Controlled Trial. Iwanoff, C., Salamon, C.[2020]

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 50 patients undergoing vaginal reconstructive surgery, liposomal bupivacaine (LB) did not show any significant advantage over plain bupivacaine in terms of postoperative pain control, narcotic use, or length of hospital stay.

Despite LB's higher cost, the results indicate that it is not more effective than plain bupivacaine for managing pain after surgery, suggesting a need for further research to find the best pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal versus plain bupivacaine for pain control following vaginal reconstruction. Jensen, S., Amasyali, AS., Keheila, M., et al.[2023]

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]

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]

In a study of 34 patients undergoing breast augmentation, liposomal bupivacaine provided statistically significant lower pain scores compared to standard bupivacaine at multiple time points post-surgery, indicating it may offer better pain control.

Despite the statistical significance, the differences in pain relief were small, and 70% of patients felt the additional cost of liposomal bupivacaine was not justified by the benefits, suggesting limited clinical relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. Nadeau, MH., Saraswat, A., Vasko, A., et al.[2022]

In a study involving patients undergoing robot-assisted hysterectomy, the use of liposomal bupivacaine in subcostal TAP blocks significantly reduced total opioid use in the first 72 hours post-surgery compared to standard bupivacaine.

Patients receiving liposomal bupivacaine reported lower maximum pain scores and had a decreased incidence of nausea and vomiting, suggesting improved overall satisfaction and comfort after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound guided subcostal transversus abdominis plane (TAP) infiltration with liposomal bupivacaine for patients undergoing robotic assisted hysterectomy: A prospective randomized controlled study. Hutchins, J., Delaney, D., Vogel, RI., et al.[2022]

References

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

Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. [2021]

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

Liposomal Bupivacaine Versus Bupivacaine Hydrochloride with Lidocaine during Midurethral Sling Placement: A Randomized Controlled Trial. [2020]

3. England pubmed.ncbi.nlm.nih.gov

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

4. Canada pubmed.ncbi.nlm.nih.gov

Liposomal versus plain bupivacaine for pain control following vaginal reconstruction. [2023]

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

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

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

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

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. England pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. [2022]

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

Ultrasound guided subcostal transversus abdominis plane (TAP) infiltration with liposomal bupivacaine for patients undergoing robotic assisted hysterectomy: A prospective randomized controlled study. [2022]

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

Paravertebral Nerve Block With Liposomal Bupivacaine for Pain Control Following Video-Assisted Thoracoscopic Surgery and Thoracotomy. [2020]

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

Impact of liposome bupivacaine on the adequacy of pain management and patient experiences following aesthetic surgery: Results from an observational study. [2020]