Bupivacaine Liposomes or Bupivacaine for CMB on Postoperative Analgesia in Laparoscopic Hepatobiliary Pancreatic Surgery

Effect of Bupivacaine Liposomes or Bupivacaine for Ultrasound-guided CMB on Postoperative Analgesia in Laparoscopic Hepatobiliary Pancreatic Surgery: a Prospective, Single Blind, Completely Randomized, Active Controlled Clinical Trial

Numerous studies have confirmed that regional analgesia using peripheral nerve block has great potential for perioperative analgesia in abdominal surgery. Ultrasound guided costal margin block (CMB) is a new regional anesthesia technique that has been proven to compensate for the analgesic effects of regional analgesia techniques such as transverse abdominal muscle plane (TAP) and rectus abdominis sheath (RSB) on mid abdominal incisions, but it is difficult to meet the analgesic needs of anterior and outer abdominal wall incisions. According to relevant anatomy and research, the application of local anesthetics along the rib margin under the rectus abdominis muscle or under the external oblique muscle on the rib surface can block the lateral and anterior cutaneous branches of the thoracoabdominal nerve, known as CMB. Ultrasound guided CMB requires the injection of local anesthetics onto the surface of the rib along the plane below the rectus abdominis and oblique muscles, covering most of the upper abdominal incision pain. However, there are few reports on other types of upper abdominal surgeries such as liver, gallbladder, and pancreas surgeries.

Bupivacaine liposomes are an important innovation, which encapsulate bupivacaine in polycystic liposomes using DepoFoam technology to achieve slow drug release and effectively prolong pain relief time by up to 72 hours. This ultra long acting local anesthetic has significant advantages in reducing opioid use, improving analgesic satisfaction, reducing complications, and shortening hospital stays, and has been applied in the ERAS concept.

The investigators designed a prospective, single blind, randomized, active controlled clinical trial to investigate the effect of bupivacaine liposomes in combination with bupivacaine mixture or bupivacaine alone for ultrasound-guided bilateral CMB on postoperative analgesia in patients undergoing laparoscopic hepatobiliary pancreatic surgery. Our main hypothesis is that the use of bupivacaine liposomes and a mixture of bupivacaine for ultrasound-guided CMB in a multimodal analgesia regimen can more effectively reduce the dosage of intravenous patient-controlled analgesia (PCA) opiates within 72 hours after laparoscopic hepatobiliary pancreatic surgery compared to using bupivacaine alone. Secondary outcomes include the dosage of PCA opiates within 24-48 hours, pain score values, patient satisfaction, adverse reactions, and complications.

Study Overview

• Status: Not yet recruiting
• Conditions: Analgesia, Postoperative; Opioids; Bupivacaine; Ultrasound-Guided
• Intervention / Treatment: Drug: Bupivacaine Liposomes(BL); Drug: Bupivacaine(B)

Detailed Description

All participators were randomized into two groups using a complete randomization allocation method: the trial group and the control group. An investigator introduced the study to the study before surgery and informed consent was obtained. The investigators educate patients on how to use the VAS scale to express pain intensity and instruct patients on how to use the postoperative analgesia pump. General anesthesia with endotracheal intubation or laryngeal mask before the nerve block. Standard analgesic protocol: sufentanil (0.5 μg/ kg) + remifentanil (0.1-0.2 μg / kg/min) + flurbiprofen ester (50mg); intravenous analgesia pump (PCIA) or analgesic with opioids and non-steroidal anti-inflammatory drugs as needed. All patients underwent ultrasound-guided bilateral costal margin block (CMB). Test group: 20ml bupivacaine liposomes +10ml 0.75% bupivacaine hydrochloride + 20ml normal saline, for ultrasound-guided CMB. Control group: 10 ml of 0.75% bupivacaine hydrochloride + 40ml of normal saline, with ultrasound-guided CMB.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Li Xu, MD; Phone Number: 86-13277070358; Email: 65022661@qq.com
• Study Contact Backup: Name: Wei Mei., MD; Phone Number: 86-027-83665481

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. 1095 Jiefang Avenue, Wuhan City, Hubei Province
      • Contact: Li Xu, MD; Phone Number: 86-027-83663173; Email: 65022661@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-80 years old ASA Level I-III Laparoscopic Hepatobiliary Pancreatic Surgery

Exclusion Criteria:

• Body Mass Index (BMI) ≥ 30 kg/m ² or ≤ 15 kg/m ² Known alcohol or drug abuse History of upper abdominal surgery Congenital coagulation dysfunction Localized or systemic infection Peripheral neuropathy Unable to understand the research plan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bupivacaine liposomes(BL); 20ml of bupivacaine liposomes + 10ml 0.75% bupivacaine hydrochloride + 20ml normal saline for ultrasound-guided bilateral costal margin block. Block method: First, the high-frequency ultrasound probe is placed in the direction of the parasternal line parallel to the costal edge, and find the image of the costal cartilage and rectus abdominis space 。The needle was inserted along the medial side of the rectus to the lateral plane, and 15 ml of local anesthetic was injected between the costal cartilage and rectus abdominis space 。The ultrasound probe was then moved along the costal margin to the axillary front, flush with the tenth rib, and 10 ml of local anesthetic was injected in the plane between the tenth rib and the extraabdominal oblique muscle 。Similarly, perform ultrasound-guide costal rim block on the other side.	Drug: Bupivacaine Liposomes(BL); 20ml of bupivacaine liposomes (266mg) + 10 ml of bupivacaine 0.75% hydrochloride + 20ml saline for ultrasound guided CMB.
Active Comparator: bupivacaine(B); 10 ml of 0.75% bupivacaine hydrochloride + 40ml normal saline for ultrasound-guided bilateral costal margin block in the same method as the experimental group	Drug: Bupivacaine(B); 10 ml of 0.75% bupivacaine hydrochloride + 40ml normal saline for ultrasound-guided bilateral costal margin block

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Opioid Consumption	Main outcome measure: Postoperative 72 hour intravenous patient-controlled analgesia opioid dosage.	up to 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity	Pain intensity will be assessed using the Numerical Rating Scale (NRS), a 0-10 scale where 0 represents no pain and 10 represents the worst imaginable pain. Pain intensity will be measured during rest (supine position) and activity (shifting from supine position to lateral position) at 5 time points: at Post Anesthesia Care Unit(PACU), 6 hours, 24 hours, 48 hours，and 72 hours post-surgery	up to 3 days
Cumulative use of opioid drugs	Cumulative use of opioid drugs for 24-48 hour intravenous patient-controlled analgesia	up to 2 days
Other indicators	The incidence of postoperative pulmonary complications (including pneumonia, hypoxemia, and atelectasis), postoperative sleep quality (Pittsburgh Sleep Quality Scale), patient satisfaction with postoperative analgesic treatment (0-10 scale, 0 for very dissatisfied, 10 for very satisfied), time of first ambulation after surgery, time of first anal exhaust after surgery, length of hospital stay, and adverse events such as opioid related dizziness, nausea, and vomiting, as well as block related complications.	through study completion, an average of 10 day

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology
• Investigators: Principal Investigator: Wei Mei, MD, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Estimated): October 8, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 15, 2024
• First Posted (Actual): December 17, 2024

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Bupivacaine Liposome; Costal Margin Block; Laparoscopic Hepatobiliary Pancreatic Surgery
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia; Physiological Effects of Drugs; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Bupivacaine
• Other Study ID Numbers: Tongji Hospital 20241030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: individual participant data sets to be shared will include all collected individual participant data that underlie the results reported in any publications resulting from the trial. This would typically include data related to pain relief, opioid analgesic consumption, incidence of complications, and any other relevant outcomes assessed at multiple time points within 72 hours after surgery.
• IPD Sharing Time Frame: From February 1,2025 to February 1,2027
• IPD Sharing Access Criteria: The IPD and any additional supporting information will be shared with qualified researchers upon request. Access will be granted for the purpose of conducting further analyses related to the outcomes of the clinical trial, such as but not limited to, pain relief, opioid analgesic consumption, and complications. Requests for access will be reviewed by the principal investigators and designated research personnel to ensure that the proposed analyses align with the objectives of the study and maintain participant confidentiality. Access to the data will be provided through a secure mechanism that safeguards the privacy and integrity of the individual participant data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No