Liposomal Bupivacaine for Post-Cesarean Pain

Overseen By Antonio Gonzalez, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Yale University

Disqualifiers: Magnesium sulfate, NICU admission, 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

147 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The TAP block offers analgesia by blocking the sensory nerves of the anterior abdominal wall. The procedure is performed under ultrasound guidance, after identification of the external oblique, internal oblique and transverse abdominis muscle. Medication is injected in the neurofascial plane between the internal oblique and the tranversus abdominis muscle. Previous studies have demonstrated limited (\<24 hour) effect of the block when compared to the use of intrathecal morphine (considered to be the "gold standard" for postoperative analgesia). In a study by McMarrow et al., post-caesarian pain control combinations including TAP blocks with local anesthetic (Bupivacaine) or saline after a spinal anesthetic with or without intrathecal morphine were compared. At 6 hours the Morphine consumption was slightly reduced in the patients that received both intrathecal morphine and TAP blocks with LA when compared to patients that received spinal saline and TAP with saline. At 24 hours the TAP block conferred no benefit in terms of opioid consumption. Similarly, the study by Lee et al. demonstrated better pain scores for the first 2 hours in patients receiving both intrathecal morphine and a TAP block with ropivacaine. At 24 hours there was no difference in the pain scores for patients that received both intrathecal morphine and TAP blocks. On the contrary, a more recent study utilizing liposomal bupivacaine has been utilized for TAP blocks for post cesarean delivery analgesia, demonstrating opioid reductions for up to 72 hours. Liposomal bupivacaine is a novel, multivesicular formulation designed for rapid absorption, prolonged release of bupivacaine, and analgesia following a single intra-operative administration into the surgical wound or for TAP blocks. Current anesthesia practices encourage the use of multimodal analgesia that aim at enhanced recovery after surgery (ERAS). The ERAS model aims to decrease immobility, pain and post-operative ileus. Pain and immobility may be closely related, and the latter has rarely been monitored in the post-operative setting. It is planned to use a research validated fit-bit like device (Actigraph GT3-X) to monitor patient steps (mobility).

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 are using opioids, you may not be eligible to participate.

Is liposomal bupivacaine safe for use in humans?

Research suggests that liposomal bupivacaine is generally safe for use in humans, as studies have not reported significant adverse events when used for pain relief in various surgical procedures. ^{1 2 3 4 5}

How is the drug liposomal bupivacaine different for post-cesarean pain?

Liposomal bupivacaine is unique because it is a long-acting form of bupivacaine that is encapsulated in tiny fat-like particles, allowing it to provide extended pain relief compared to regular bupivacaine. This can help reduce the need for opioids after a cesarean delivery. ^{2 6 7 8 9}

What data supports the effectiveness of the drug Liposomal Bupivacaine for Post-Cesarean Pain?

Research shows that using liposomal bupivacaine in a TAP block can reduce postoperative pain and the need for opioids after surgery. Additionally, adding dexamethasone to bupivacaine in a TAP block may improve pain relief and extend the duration of pain control. ^{4 5 6 7 10}

Who Is on the Research Team?

Antonio Gonzalez, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for women aged 18-45 undergoing cesarean delivery without allergies to morphine or bupivacaine, no anxiety history, and no recent/chronic opioid use. They should be generally healthy (ASA-1 to ASA-3). Overweight individuals (BMI > 45), those needing magnesium sulfate therapy, additional surgeries beyond cesarean or whose newborns require intensive care are excluded.

Inclusion Criteria

I have not used opioids recently or regularly.

You are not allergic to bupivacaine.

You are not allergic to morphine.

Exclusion Criteria

I need surgery beyond a C-section and possibly tying my tubes.

I need Magnesium sulfate treatment.

My BMI is over 45.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive spinal anesthesia and a TAP block with either liposomal bupivacaine, bupivacaine, or a control procedure during cesarean delivery

Immediate post-operative period

1 visit (in-person)

Post-operative Monitoring

Participants are monitored for pain management and recovery using ObsQoR-11 surveys and step counts

72 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Dexamethasone and Methylprednisolone
• Liposomal Bupivacaine
• TAP Block

Trial Overview The study tests the effectiveness of a TAP block using Liposomal Bupivacaine (LB) versus standard Bupivacaine and steroids for post-cesarean pain relief. It aims to reduce opioid use by providing prolonged pain control with LB compared to short-term effects seen with traditional methods.

How Is the Trial Designed?

Group I: Liposomal Bupivacaine Experimental Treatment 2 Interventions

Patient will receive intrathecal morphine + TAP block with Liposomal bupivacaine and bupivacaine 0.25%

Group II: Control group (Bupivacaine) Active Control 1 Intervention

Patient will receive intrathecal morphine and TAP block with plain bupivacaine.

Group III: Bupivacaine + dexamethasone and methylprednisolone Active Control 1 Intervention

Patient will receive intrathecal morphine + TAP block with only bupivacaine.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

In a study of 58 patients undergoing cesarean sections, adding 8 mg of perineural dexamethasone to bupivacaine during a TAP block significantly prolonged the time to first request for pain relief medication to 8.5 hours compared to 5.3 hours for bupivacaine alone.

Patients receiving dexamethasone also reported lower pain intensity scores at 6, 12, and 24 hours post-surgery and required less total analgesic medication over 24 hours, indicating improved pain management without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of perineural dexamethasone and transverse abdominal plane block for postoperative analgesia in cesarean section operations under spinal anesthesia: an observational study. Aga, A., Abrar, M., Ashebir, Z., et al.[2022]

In a study involving 60 patients undergoing abdominal surgery, adding dexamethasone to bupivacaine for a TAP block significantly reduced postoperative pain at 2, 4, and 12 hours compared to bupivacaine alone.

The combination of dexamethasone and bupivacaine not only prolonged the time to first analgesia but also resulted in lower morphine consumption and reduced nausea and vomiting, indicating a safer and more effective pain management strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of adding dexamethasone to bupivacaine on transversus abdominis plane block for abdominal hysterectomy: A prospective randomized controlled trial. Ammar, AS., Mahmoud, KM.[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]

In a study of 287 patients undergoing colorectal surgery, the timing of transversus abdominis plane (TAP) blocks with liposomal bupivacaine (before or after anesthesia induction) did not significantly affect postoperative pain scores or opioid consumption.

However, patients who received TAP blocks after surgery required more ketorolac, indicating that while timing may not impact pain control, it could influence the use of additional non-opioid analgesics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing of Transversus Abdominis Plane Block and Postoperative Pain Management. Escudero-Fung, M., Lehman, EB., Karamchandani, K.[2022]

In a study of 76 patients undergoing outpatient arthroscopic rotator cuff repair, liposomal bupivacaine (LB) significantly reduced postoperative narcotic consumption compared to conventional bupivacaine combined with dexamethasone, indicating its effectiveness in pain management.

Both LB and LB combined with dexamethasone showed similar outcomes in narcotic use, suggesting that LB alone is sufficient for effective pain control, which can help decrease reliance on narcotics after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Shot Liposomal Bupivacaine Reduces Postoperative Narcotic Use Following Outpatient Rotator Cuff Repair: A Prospective, Double-Blinded, Randomized Controlled Trial. Baessler, AM., Moor, M., Conrad, DJ., et al.[2021]

Incorporating dexamethasone into bupivacaine-loaded microspheres significantly prolongs the duration of motor block, making it a promising enhancement for pain management in clinical settings.

While dexamethasone alone does not cause motor block, its addition to bupivacaine can delay the onset of motor block without affecting the drug's pharmacokinetics, suggesting a complex interaction that could optimize anesthesia outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dexamethasone on motor brachial plexus block with bupivacaine and with bupivacaine-loaded microspheres in a sheep model. Estebe, JP., Le Corre, P., Clément, R., et al.[2019]

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 of 60 patients undergoing donor nephrectomy, subcostal TAP blocks using liposomal bupivacaine resulted in significantly lower maximal pain scores compared to non-liposomal bupivacaine at 24-72 hours post-injection.

Patients receiving liposomal bupivacaine also required less opioid medication (fentanyl) in the 48-72 hour period after surgery, indicating better pain management with liposomal bupivacaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-guided subcostal transversus abdominis plane blocks with liposomal bupivacaine vs. non-liposomal bupivacaine for postoperative pain control after laparoscopic hand-assisted donor nephrectomy: a prospective randomised observer-blinded study. Hutchins, JL., Kesha, R., Blanco, F., et al.[2022]

In a study of 186 women undergoing cesarean delivery, the use of a transversus abdominis plane (TAP) block with long-acting liposomal bupivacaine (LB) plus bupivacaine HCl significantly reduced total opioid consumption compared to bupivacaine HCl alone, with a mean difference of -16.5 mg over 72 hours.

The addition of LB did not increase pain intensity compared to bupivacaine HCl alone, supporting its efficacy in reducing opioid use without compromising pain management, although a slightly higher percentage of patients experienced adverse events in the LB group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transversus Abdominis Plane Block With Liposomal Bupivacaine for Pain After Cesarean Delivery in a Multicenter, Randomized, Double-Blind, Controlled Trial. Nedeljkovic, SS., Kett, A., Vallejo, MC., et al.[2022]

Liposomal bupivacaine (LB) used in a transversus abdominis plane (TAP) block, either alone or with intrathecal morphine (ITM), resulted in similar opioid consumption compared to ITM alone for pain management after cesarean delivery, indicating its effectiveness as an analgesic option.

Both LB groups experienced significantly less pruritus (itchiness) compared to the ITM group, suggesting that LB may offer a safer profile with fewer side effects in postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of transversus abdominis plane block with liposomal bupivacaine after cesarean delivery with or without intrathecal morphine. Habib, AS., Nedeljkovic, SS., Horn, JL., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

The use of perineural dexamethasone and transverse abdominal plane block for postoperative analgesia in cesarean section operations under spinal anesthesia: an observational study. [2022]

2. India pubmed.ncbi.nlm.nih.gov

Effect of adding dexamethasone to bupivacaine on transversus abdominis plane block for abdominal hysterectomy: A prospective randomized controlled trial. [2022]

3. 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]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Timing of Transversus Abdominis Plane Block and Postoperative Pain Management. [2022]

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

Single-Shot Liposomal Bupivacaine Reduces Postoperative Narcotic Use Following Outpatient Rotator Cuff Repair: A Prospective, Double-Blinded, Randomized Controlled Trial. [2021]

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

Effect of dexamethasone on motor brachial plexus block with bupivacaine and with bupivacaine-loaded microspheres in a sheep model. [2019]

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

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

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

Ultrasound-guided subcostal transversus abdominis plane blocks with liposomal bupivacaine vs. non-liposomal bupivacaine for postoperative pain control after laparoscopic hand-assisted donor nephrectomy: a prospective randomised observer-blinded study. [2022]

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

Transversus Abdominis Plane Block With Liposomal Bupivacaine for Pain After Cesarean Delivery in a Multicenter, Randomized, Double-Blind, Controlled Trial. [2022]

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

Randomized trial of transversus abdominis plane block with liposomal bupivacaine after cesarean delivery with or without intrathecal morphine. [2022]