The Efficacy and Safety of Liposomal Bupivacaine in Relieving Postoperative Pain After Laparoscopic Surgery

The Efficacy and Safety of Liposomal Bupivacaine Plus Bupivacaine Local Incisional Infiltration for Postoperative Pain in Patients Undergoing Laparoscopic Surgery:A Multi-Center Randomized Controlled Trial

Compared with traditional laparotomy, laparoscopic surgery offers advantages including minimal invasiveness, accelerated patient recovery, and reduced hospital stay. Although postoperative incision pain is generally less severe than that following laparotomy, it remains a notable clinical issue that impedes patient recovery. The majority of patients report incisional discomfort, with approximately 30% to 50% requiring oral analgesics to alleviate pain symptoms. Within the first two days after laparoscopic procedures, most patients experience varying degrees of incisional pain, with peak intensity typically occurring within hours after surgery and gradually subsiding over two to three days. Studies indicate that local infiltration anesthesia at the surgical site significantly ameliorates postoperative incision pain, enhances analgesic efficacy, and shortens recovery time in patients undergoing laparoscopic surgery.Liposomal bupivacaine(LB) is a novel, long-acting, sustained-release amide-type local anesthetic, providing localized analgesic effects for up to 72 hours. Some researchers have reported the analgesic effects of LB VS traditional local anesthetics infiltration, but the current research results are highly heterogeneous. More prospective studies are needed to evaluate whether LB infiltration is superior to the traditional local anesthetics for the management of postoperative pain. The investigators designed this study to compare the analgesic effect of using LB plus bupivacaine for local infiltration with bupivacaine along for patients after laparoscopic surgery.

Study Overview

• Status: Recruiting
• Conditions: Laparoscopic Surgery; Local Infiltration; Liposomal Bupivacaine
• Intervention / Treatment: Drug: Bupivacaine hydrochloride; Drug: Liposomal bupivacaine plus bupivacaine

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fang Luo; Phone Number: +86 13611326978; Email: 13611326978@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100070
      • Recruiting
      • Beijing Tiantan Hospital
      • Contact: Fang Luo; Phone Number: +86 13611326978; Email: 13611326978@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients scheduled for elective laparoscopic cholecystectomy, hernia repair, and appendectomy under general anesthesia;
2. Ages 18 to 64 years old；
3. American Society of Anesthesiologists (ASA) physical status of I-III；
4. Glasgow Coma Scale (GCS) score of 15；
5. Patients must be able to understand the nature and potential personal consequences of the clinical trial, signing of the informed consent form.

Exclusion Criteria:

1. History of chronic pain syndrome of any cause.
2. Patients with heart conduction block (sinus block or atrioventricular block).
3. Patients with unstable coronary artery disease.
4. Patients with gastric ulcer or gastric bleeding.
5. Patients with diabetes and are being treated with insulin.
6. Subjects with coagulation dysfunction (prothrombin time or activated partial thromboplastin time is higher than the normal threshold) or patients who are taking oral anticoagulants for other medical reasons and have not stopped it before surgery, such as warfarin or new anticoagulants rivaroxaban or dabigatran.
7. Patients with abnormal liver function: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2× the upper limit of normal (ULN) or total bilirubin (TBIL) ≥ 1.5×ULN.
8. Patients with renal impairment (serum creatinine > 176 µmol/L) or receiving dialysis treatment within 28 days before surgery.
9. Patients with a history of diagnosed mental illness or currently taking psychotropic medication.
10. Excessive alcohol or drug abuse, chronic opioid use (more than 2 weeks or 3 days per week for more than 1 month), use of drugs with confirmed or suspected sedative or analgesic effects, or use of any painkiller within 24 h before surgery.
11. Pregnancy or breastfeeding.
12. Extreme body mass index (BMI) (< 15 or > 35).
13. Participation in another interventional trial that interferes with the intervention or outcome of this trial.
14. Patients with a history of allergy to local anaesthetics or one of the study drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bupivacaine hydrochloride	Drug: Bupivacaine hydrochloride; The 40 mL 0.25% Bupivacaine hydrochloride (100 mg, normal saline dilution) for the Bupivacaine hydrochloride group.Local infiltration will be performed by the surgeon before closure. A total of 30mL of fluid will be injected at the incision.The PCA solution is prepared by diluting 100 μg of sufentanil and 16 mg of ondansetron with normal saline to a total volume of 100 mL. Postoperatively, the patient may press the demand button for analgesia. Each activation delivers a 2 mL bolus, with a lockout interval of 10 minutes.If analgesia remains inadequate after four consecutive demands, one Oxycodone and Acetaminophen Tablets (containing 5 mg oxycodone hydrochloride and 325 mg acetaminophen) is administered orally, with a minimum interval of 6 hours between repeated administrations. If pain persists, intravenous morphine 5 mg may be administered at intervals no shorter than 4 hours.
Experimental: Liposomal bupivacaine plus bupivacaine	Drug: Liposomal bupivacaine plus bupivacaine; The 20 mL (266 mg) of liposomal bupivacaine will be mixed with a volume of 20 mL 0.25% Bupivacaine hydrochloride (50 mg, normal saline dilution) for the Liposomal Bupivacaine plus Bupivacaine hydrochloride group.Local infiltration will be performed by the surgeon before closure. A total of 30mL of fluid will be injected at the incision.The PCA solution is prepared by diluting 100 μg of sufentanil and 16 mg of ondansetron with normal saline to a total volume of 100 mL. Postoperatively, the patient may press the demand button for analgesia. Each activation delivers a 2 mL bolus, with a lockout interval of 10 minutes.If analgesia remains inadequate after four consecutive demands, one Oxycodone and Acetaminophen Tablets (containing 5 mg oxycodone hydrochloride and 325 mg acetaminophen) is administered orally, with a minimum interval of 6 hours between repeated administrations. If pain persists, intravenous morphine 5 mg may be administered at intervals no shorter than 4 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Intravenous Morphine Equivalents of Rescue Analgesic Medications Within 48 Hours Postoperatively	The postoperative period 48 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (AUC) of Numeric Rating Scale at rest (NRSr) Within 0-72 Hours Postoperatively	The Numeric Rating Scale (NRS) designates 0 as representing no pain and 10 as representing the most severe pain; scores of 1-3 indicate mild pain, 4-6 denote moderate pain, and 7-10 signify severe pain.	Data will be collected at 2 hours, 24 hours, 48 hours, and 72 hours postoperatively.
Numeric Rating Scale at rest (NRSr) at 1 week, 1 month, and 3 months postoperatively	The Numeric Rating Scale (NRS) designates 0 as representing no pain and 10 as representing the most severe pain; scores of 1-3 indicate mild pain, 4-6 denote moderate pain, and 7-10 signify severe pain.	Postoperative day 7, month 1, and month 3.
Time to request of first analgesia		Within 48 hours postoperatively.
Cumulative sufentanil dose for four separate periods (0-4, 4-8, 8-24, and 24-48 h), a total press count including both valid and invalid presses		Postoperative Hours 4, 8, 24, and 48.
Duration days of Oral Oxycodone and Acetaminophen Tablets Administration		Within 3 months postoperatively.
Patient Satisfaction Scale，PSS	On a scale ranging from 0 to 10, where 0 denotes "completely dissatisfied" and 10 signifies "extremely satisfied."	Postoperative hours 2, 24, 48, and 72; week 1; month 1; and month 3.
Ramsay Sedation Scale，RSS	The RSS utilizes a six-point scale to evaluate sedation levels. The total score ranges from 1 to 6 as follows: anxious or agitated (1 point); oriented, calm, and cooperative (2 points); responsive to commands (3 points); drowsy with brisk response to glabellar tap or loud auditory stimulus (4 points); drowsy with sluggish response to glabellar tap or loud auditory stimulus (5 points)；and drowsy with no response whatsoever（6）points. A score of 1 reflects inadequate sedation, scores of 2 to 4 indicate satisfactory sedation, while scores of 5 to 6 denote oversedation.	Postoperative at 2 hours, 24 hours, 48 hours, and 72 hours.
Quality of Recovery-40，QoR-40	The Quality of Recovery-40 (QoR-40) serves as a globally recognized metric for evaluating the quality of recovery. It encompasses five dimensions-emotional state, physical comfort, physiological independence, psychological support, and pain-comprising a total of 40 items, each rated on a 1-5 scoring scale. The overall QoR-40 score ranges from 40 (indicating extremely poor recovery quality) to 200 (representing excellent recovery quality).	Postoperative hours 24, 48, and 72.
The length of stay in the post-anesthesia care unit（PACU）	The time from the end of surgery until the patient regains consciousness and has stable vital signs after extubating and is subsequently transferred back to the ward.	The time from the end of surgery until transferred back to the ward.Typically, patients are transferred back to the ward after approximately 30 to 60 minute.
Length of Stay (LOS)		Perioperation.
Total hospitalization expenses incurred during the patient's inpatient stay		Perioperation.
Postoperative nausea and vomiting，PONV		Postoperatively within 72 hours.
Adverse events，AEs	Systemic Toxicity of Local Anesthetics (LAST), localized hematoma, pruritus, hypotension, arrhythmia, delirium, etl.	Within 72 hours postoperatively.
Area under the curve (AUC) of the Numerical Rating Scale during movement (NRSm) within 0-72 hours postoperatively	The Numeric Rating Scale (NRS) designates 0 as representing no pain and 10 as representing the most severe pain; scores of 1-3 indicate mild pain, 4-6 denote moderate pain, and 7-10 signify severe pain.	Data will be collected at 2 hours, 24 hours, 48 hours, and 72 hours postoperatively.
Numeric Rating Scale during movement (NRSm) at 1 week, 1 month, and 3 months postoperatively	The Numeric Rating Scale (NRS) designates 0 as representing no pain and 10 as representing the most severe pain; scores of 1-3 indicate mild pain, 4-6 denote moderate pain, and 7-10 signify severe pain.	Postoperative day 7, month 1, and month 3.
Total dosage of orally oxycodone and acetaminophen tablets		Within 3 months postoperatively.

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Publications and helpful links

General Publications

• Keller DS, Tahilramani RN, Flores-Gonzalez JR, Ibarra S, Haas EM. Pilot study of a novel pain management strategy: evaluating the impact on patient outcomes. Surg Endosc. 2016 Jun;30(6):2192-8. doi: 10.1007/s00464-015-4459-4. Epub 2015 Aug 15.
• Suseela I, Anandan K, Aravind A, Kaniyil S. Comparison of ultrasound-guided bilateral subcostal transversus abdominis plane block and port-site infiltration with bupivacaine in laparoscopic cholecystectomy. Indian J Anaesth. 2018 Jul;62(7):497-501. doi: 10.4103/ija.IJA_55_18.
• Waddimba AC, Newman P, Shelley JK, McShan EE, Cheung ZO, Gibson JN, Bennett MM, Petrey LB. Pain management after laparoscopic appendectomy: Comparative effectiveness of innovative pre-emptive analgesia using liposomal bupivacaine. Am J Surg. 2022 May;223(5):832-838. doi: 10.1016/j.amjsurg.2021.09.019. Epub 2021 Sep 24.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2026
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 14, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Bupivacaine
• Other Study ID Numbers: KY2025-289-02-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures and appendices) are available. Derived data supporting the findings of this study are available from the corresponding author Fang Luo on request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No