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

Official title

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

Overview

Hemorrhoids represents the most prevalent condition among anorectal disorders. Due to the unique anatomical characteristics of the perianal region, patients frequently experience severe postoperative pain, which may lead some individuals to delay treatment due to pain-related anxiety. Consequently, effective postoperative pain management is critical for the recovery of hemorrhoid patients. Developing a simplified, efficient, and safe analgesic approach to alleviate postoperative pain has become an urgent issue in perioperative care. Multimodal analgesia regimens recommend the combined use of local anesthetics to synergistically reduce perioperative pain intensity. However, the primary limitation of this analgesic modality lies in the relatively short duration of action following a single injection of local anesthetic.Liposomal bupivacaine is an innovative long-acting, extended-release amide-type local anesthetic that provides analgesic efficacy for up to 72 hours. However, its efficacy and safety for local infiltration analgesia following hemorrhoid surgery have not been fully validated. Against this backdrop, the present study aims to evaluate and compare the clinical outcomes and safety profile of liposomal bupivacaine versus conventional bupivacaine for postoperative pain management via local infiltration in patients undergoing Hemorrhoid surgery.

Interventions

• Drug Bupivacaine hydrochloride
  30 mL of 0.25% bupivacaine (75 mg, diluted in normal saline) was administered as a perianal infiltration at the conclusion of the surgical procedure. Using a 22-gauge needle, the solution was injected in a fan-shaped pattern into the perianal tissues.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, wit
• Drug Liposomal bupivacaine plus bupivacaine
  At the conclusion of the surgical procedure, perianal infiltration was administered with 30 mL of local anesthetic. Using a 22-gauge needle, the solution was injected in a fan-shaped.The local anesthetic is prepared by mixing 20 mL (266 mg) of liposomal bupivacaine with 20 mL of 0.25% bupivacaine and extracting a volume of 30 mL.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 p

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.]
• 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.]
• 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 duration 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.]
• Total hospitalization expenses incurred during the patient's inpatient stay [Time frame: Perioperation.]
• Postoperative nausea and vomiting，PONV [Time frame: Postoperatively within 72 hours.]

Eligibility criteria

Inclusion criteria

• Patients scheduled for elective Hemorrhoid Surgery 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

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital — Beijing

Publications

• Cui J, Xu Q, Yu Z, Sun J, Zheng Y, Huang W, Yu Y, Gao S, Wang Z, Zhang S. Local infiltration of HYR-PB21, a sustained-release formulation of bupivacaine, provides analgesia and reduces opioid requirement after haemorrhoidectomy: a randomised controlled trial. Br J Anaesth. 2022 Dec;129(6):970-976. doi: 10.1016/j.bja.2022.08.035. Epub 2022 Oct 13. PMID 36243580
• Chitty L, Ridley B, Johnson B, Ibrahim M, Mongan PD, Hoefnagel AL. Liposomal compared to 0.25% bupivacaine in patients undergoing hemorrhoidectomy: A pre- and post-implementation quality improvement evaluation. J Clin Anesth. 2022 Sep;80:110868. doi: 10.1016/j.jclinane.2022.110868. Epub 2022 Apr 29. PMID 35500430

Identifiers

NCT: NCT07442539 · KY2025-289-02-3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗