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

Official title

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

Overview

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.

Interventions

• 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 lockou
• 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 patien

Primary outcome measures

• Intravenous Morphine Equivalents of Rescue Analgesic Medications Within 48 Hours Postoperatively [Time frame: The postoperative period 48 hours.]

Secondary outcome measures (12)

• Area Under the Curve (AUC) of Numeric Rating Scale at rest (NRSr) Within 0-72 Hours Postoperatively [Time frame: Data will be collected at 2 hours, 24 hours, 48 hours, and 72 hours postoperatively.]
• Area under the curve (AUC) of the Numerical Rating Scale during movement (NRSm) within 0-72 hours postoperatively [Time frame: 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 [Time frame: Postoperative day 7, month 1, and month 3.]
• Numeric Rating Scale during movement (NRSm) at 1 week, 1 month, and 3 months postoperatively [Time frame: Postoperative day 7, month 1, and month 3.]
• Time to request of first analgesia [Time frame: 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 [Time frame: Postoperative Hours 4, 8, 24, and 48.]
• Duration days of Oral Oxycodone and Acetaminophen Tablets Administration [Time frame: Within 3 months postoperatively.]
• Patient Satisfaction Scale，PSS [Time frame: Postoperative hours 2, 24, 48, and 72; week 1; month 1; and month 3.]
• Ramsay Sedation Scale，RSS [Time frame: Postoperative at 2 hours, 24 hours, 48 hours, and 72 hours.]
• Quality of Recovery-40，QoR-40 [Time frame: Postoperative hours 24, 48, and 72.]
• The length of stay in the post-anesthesia care unit（PACU） [Time frame: 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) [Time frame: Perioperation.]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• History of chronic pain syndrome of any cause.
• Patients with heart conduction block (sinus block or atrioventricular block).
• Patients with unstable coronary artery disease.
• Patients with gastric ulcer or gastric bleeding.
• Patients with diabetes and are being treated with insulin.
• 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.
• 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.
• Patients with renal impairment (serum creatinine > 176 µmol/L) or receiving dialysis treatment within 28 days before surgery.
• Patients with a history of diagnosed mental illness or currently taking psychotropic medication.
• 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.
• Pregnancy or breastfeeding.
• Extreme body mass index (BMI) (< 15 or > 35).
• Participation in another interventional trial that interferes with the intervention or outcome of this trial.
• Patients with a history of allergy to local anaesthetics or one of the study drugs.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

China · 1 center

• Beijing Tiantan Hospital — Beijing

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. PMID 26275549
• 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. PMID 34610868
• 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. PMID 30078851

Identifiers

NCT: NCT07458256 · KY2025-289-02-4

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗