Pain Control Methods for Pancreatic Cancer Surgery

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Chronic opioids

Disqualifiers: Coagulopathy, Local anesthetic allergy, 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: Unknown

Duration: Up to 96 hours

78 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. However, if you are using chronic opioids, you may not be eligible to participate.

What data supports the effectiveness of the drug liposomal bupivacaine for pain control in pancreatic cancer surgery?

Research shows that liposomal bupivacaine can reduce the need for narcotics and improve recovery outcomes, such as earlier bowel function and shorter hospital stays, in patients undergoing abdominal surgeries. This suggests it may be effective for pain control in pancreatic cancer surgery as well. ^{1 2 3 4 5}

Is liposomal bupivacaine safe for use in humans?

Liposomal bupivacaine (Exparel) has been shown to be safe in various surgical settings, including pediatric patients and those undergoing breast reconstruction, with improved pain control and reduced need for narcotics. ^{1 2 6 7 8}

How does the treatment for pain control in pancreatic cancer surgery using Rectus Sheath Block with Liposomal Bupivacaine differ from other treatments?

This treatment is unique because it uses liposomal bupivacaine, a long-acting local anesthetic, which can provide extended pain relief and reduce the need for narcotics after surgery. Unlike traditional methods, it focuses on minimizing opioid use, which can lead to fewer side effects and potentially faster recovery. ^{1 2 3 9 10}

What is the purpose of this trial?

This phase II trial compares the effect of rectus sheath block with liposomal bupivacaine to thoracic epidural analgesia (TEA) on pain control in patients following surgical removal of all or part of the pancreas and duodenectomy (pancreatoduodenectomy). Administering long acting local anesthetics, such as liposomal bupivacaine, in between the muscle layers of the abdomen (rectus sheath block) may help with pain relief during and after surgery. TEA uses a needle to insert a flexible plastic catheter into the thoracic spine to administer anesthetic and pain medication, such as bupivacaine and hydromorphone, to treat pain in the thoracic and upper abdominal areas during and after surgery. Epidurals have been successfully used to treat pain after surgery, however, it does have a risk of low blood pressure which may limit the use in the thoracic approach. Rectus sheath blocks with liposomal bupivacaine may be as effective as TEA in reducing pain in patients following a pancreatoduodenectomy.

Research Team

James Flaherty

Principal Investigator

University of Minnesota Masonic Cancer Center

Eligibility Criteria

This trial is for patients undergoing pancreatoduodenectomy, a surgery for pancreatic and duodenal tumors. Participants must be eligible for the surgical procedure and fit enough to receive either of the pain control methods being tested.

Inclusion Criteria

I am 18 or older and will have a specific pancreatic surgery at the University of Minnesota.

Exclusion Criteria

Patients unable to understand the quality of recovery survey due to intellectual barriers (to be determined by the primary investigator/attending anesthesiologist's discretion)

Patient refusal and those who have opted out of research

Pregnant patients (will be assessed through review of the medical record)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Patients undergo either thoracic epidural analgesia or rectus sheath block with liposomal bupivacaine prior to pancreatoduodenectomy

Up to 96 hours

In-hospital stay

Follow-up

Participants are monitored for opioid consumption, pain scores, and return of bowel function

Up to 7 days

In-hospital monitoring

Treatment Details

Interventions

• Rectus Sheath Block with Liposomal Bupivacaine
• Thoracic Epidural Analgesia

Trial Overview The study compares rectus sheath block with liposomal bupivacaine—a long-acting local anesthetic—against thoracic epidural analgesia (TEA), which delivers pain medication directly near the spine. The goal is to determine which method offers better post-surgery pain relief without causing low blood pressure.

Participant Groups

Group I: Group RS (rectus sheath block) Experimental Treatment 5 Interventions

Prior to pancreatoduodenectomy, patients undergo ultrasound and receive bupivacaine and liposomal bupivacaine injection into the rectus sheath.

Group II: Group E (TEA) Experimental Treatment 7 Interventions

Prior to pancreatoduodenectomy, patients undergo thoracic epidural placement and receive bupivacaine and hydromorphone continuous infusion via epidural for up to 72 hours postoperatively. Patients also receive iopamidol via epidural and undergo x-ray imaging on study.

Rectus Sheath Block with Liposomal Bupivacaine is already approved in United States, European Union for the following indications:

Approved in United States as Exparel for:

• Postsurgical pain in adults
• Local pain relief by injecting it around the edges of small to medium-sized surgical wounds

Approved in European Union as Exparel liposomal for:

• Local pain relief by injecting it around the edges of small to medium-sized surgical wounds
• Regional pain relief by injecting it around the nerves that supply the lower limbs or the shoulder

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Liposomal bupivacaine (LB) is safe for use in pediatric patients and significantly improves pain control after pharyngoplasty, as evidenced by lower pain scores compared to those receiving standard lidocaine.

Patients treated with LB had earlier oral intake, required fewer opioids, and were discharged from the hospital nearly 2 days earlier than those in the control group, highlighting its efficacy in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Pharyngoplasty. Day, KM., Nair, NM., Griner, D., et al.[2018]

In a study of 100 patients undergoing elective laparoscopic colectomy, those receiving liposomal bupivacaine TAP blocks required significantly less narcotic medication (5.06 mg) compared to those receiving standard bupivacaine (18.75 mg), indicating better pain management.

Patients treated with liposomal bupivacaine also experienced earlier bowel function (1.7 days vs 2.4 days) and shorter hospital stays (2.7 days vs 3.4 days), suggesting improved postoperative recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transversus Abdominis Plane Blocks in Laparoscopic Colorectal Surgery: Better Pain Control and Patient Outcomes with Liposomal Bupivacaine than Bupivacaine. Guerra, L., Philip, S., Lax, EA., et al.[2020]

In a study of 84 patients who underwent pancreaticoduodenectomy, the use of rectus sheath catheters (RSCs) significantly reduced postoperative opiate consumption compared to standard care, with a median reduction of 54.4 mg of oral morphine equivalents at 96 hours post-surgery.

Despite the reduced opiate use, there was no significant difference in pain scores between the RSC group and the control group, indicating that RSCs can effectively lower opiate needs without compromising pain management or increasing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectus sheath catheters reduce opiate use in pancreaticoduodenectomy: a pre- and postintervention cohort study. Tapley, PLC., Van der Vyver, M., Coburn, NG., et al.[2023]

Transversus abdominis plane (TAP) blocks with liposomal bupivacaine provided pain relief at rest that was non-inferior to epidural analgesia in patients recovering from major abdominal surgery, with a minimal difference in pain scores.

However, patients receiving TAP blocks required more opioids than those with epidurals, but experienced significantly less hypotension, suggesting TAP blocks may be safer for patients at risk of low blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transversus abdominis plane block with liposomal bupivacaine versus continuous epidural analgesia for major abdominal surgery: The EXPLANE randomized trial. Turan, A., Cohen, B., Elsharkawy, H., et al.[2022]

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 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 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 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]

Celiac plexus block (CPB) significantly reduces pain in pancreatic cancer patients, with a mean difference in pain scores of -0.42 at four weeks and -0.44 at eight weeks compared to control, indicating its efficacy as a pain management technique.

CPB also leads to lower opioid consumption, suggesting it may be a safer alternative with fewer adverse effects than traditional opioid therapies, although further research is needed to confirm its effectiveness compared to other analgesic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celiac plexus block for pancreatic cancer pain in adults. Arcidiacono, PG., Calori, G., Carrara, S., et al.[2022]

In a study of 24 patients with metastatic pancreatic cancer, both neurolytic celiac plexus block (NCPB) and epidural 5% butamben suspension (EBS) provided significant pain relief, with EBS showing a higher overall success rate (85% vs. 55%).

Both interventions were found to be safe, with no serious complications reported, and they similarly reduced opioid use, indicating that EBS is a viable alternative to NCPB for managing pain in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of epidural butamben to celiac plexus neurolytic block for the treatment of the pain of pancreatic cancer. Shulman, M., Harris, JE., Lubenow, TR., et al.[2019]

References

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

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Pharyngoplasty. [2018]

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

Transversus Abdominis Plane Blocks in Laparoscopic Colorectal Surgery: Better Pain Control and Patient Outcomes with Liposomal Bupivacaine than Bupivacaine. [2020]

3. Canada pubmed.ncbi.nlm.nih.gov

Rectus sheath catheters reduce opiate use in pancreaticoduodenectomy: a pre- and postintervention cohort study. [2023]

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

Transversus abdominis plane block with liposomal bupivacaine versus continuous epidural analgesia for major abdominal surgery: The EXPLANE randomized trial. [2022]

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

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

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

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

7. 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]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Celiac plexus block for pancreatic cancer pain in adults. [2022]

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

Comparison of epidural butamben to celiac plexus neurolytic block for the treatment of the pain of pancreatic cancer. [2019]