Liposomal Bupivacaine and Bupivacaine for TTMPB in Median Sternotomy

Liposomal Bupivacaine and Bupivacaine Alone Transverse Thoracic Muscle Plane Blocks in Median Sternotomy: a Prospective, Single-blind, Randomized Controlled Study

In light of the ongoing controversy surrounding the efficacy of bupivacaine liposomes, our study was designed to investigate, for the first time, the differential postoperative analgesic effects between bupivacaine liposomes combined with bupivacaine hydrochloride and bupivacaine hydrochloride alone in transverse thoracic muscle plane block treatment. The aim is to provide evidence-based medical guidance for drug selection in regional block local anesthesia.

Study Overview

• Status: Recruiting
• Conditions: Median Sternotomy
• Intervention / Treatment: Procedure: Transverse thoracic muscle plane block (TTMPB) using liposomal bupivacaine and bupivacaine mixture; Procedure: Transverse thoracic muscle plane block (TTMPB) using bupivacaine hydrochloride

Detailed Description

Median thoracic incision is a common method in cardiac surgery for valve replacement, coronary artery bypass and large vessel reconstruction. This kind of surgery is generally more traumatic, with obvious pain stimulation and intense stress response. Compared with other types of surgery, thoracotomy often requires larger doses of opioid analgesics, but excessive use of perioperative opioids has significant adverse effects on postoperative recovery, including sedation, constipation, nausea, addiction and respiratory depression. In addition, improper management of perioperative acute pain during thoracotomy may turn into chronic pain, which will seriously affect patients' postoperative quality of life. For pain management in thoracotomy surgery, the previous practice was to use thoracic epidural continuous catheterization to perform intradural block, but due to the narrow vertebral space in the thoracic vertebrae, this technique is difficult to operate, and for cardiac surgery, individual heparinization requirements of extracorporeal circulation during the operation may greatly increase the possibility of epidural catheter hematoma. Other studies have shown that thoracic epidural block may further lead to sympathetic block, which increases the complexity of perioperative hemodynamic management and concerns the possibility of cerebrovascular accidents.

Transversus Thoracic Plane block (TTP) is a relatively new fascial plane block method. Ultrasound visualization guidance significantly improved the safety of transversus thoracic plane block, and precise injection of local anesthesia drugs could provide perfect analgesia for the anterior branches of the second to sixth intercostal nerves. At the same time, the dosage of other analgesic drugs including opioids can be reduced to reduce the occurrence of related complications [9, 10]. Compared with multimodal analgesia alone, transverse thoracic muscle plane block can significantly reduce postoperative opioid dose. Unlike paravertebral block, the target of the transverse thoracic plane block is the distal branch of the anterior spinal nerve, so there is no risk of sympathetic block, and the injection site is far from the foramen, and there is no risk of intraspinal block or general spinal anesthesia. In view of its high effectiveness and safety, it has been successfully applied in adults and children with median thoracotomy and achieved good perioperative analgesic effects. According to the literature, the transverse thoracic plane block can also be used for the analgesic management of sternal fracture, rib fracture, sternotomy, chronic pain, and the medial incision of breast surgery.

Long-acting amide local anesthetics have been used for surgical incision infiltration anesthesia and shoulder intermuscular groove regional block anesthesia. Although bupivacaine can meet the regional anesthesia requirements for most surgeries, bupivacaine is more likely to cause serious cardiotoxicity when given the same dose as ropivacaine. Bupivacaine and ropivacaine, commonly used local anesthetics for regional block, are similar in terms of sensory action, duration, and blocking effect, but Ropivacaine has greater sensory-motor selectivity, less central nervous system and cardiac toxicity, wider safe dose range, lower reinforcement effect, and longer motor block duration. Therefore, in the current domestic regional block anesthesia technology, the application of both in regional block is more extensive.

Liposomal bupivacaine is a long-acting local anesthetic drug prepared by liposomal technology with slow-release characteristics. It has been reported that the action time of a single administration of bupivacaine liposomal is as high as 72 hours. The drug was approved by the U.S. Food and Drug Administration in October 2011 for postoperative pain management and in April 2018 for nerve block producing regional anesthesia. Compared with bupivacaine, most current research results suggest that the blocking effect of bupivacaine liposomes is not significantly superior to that of standard bupivacaine. However, other studies have suggested that bupivacaine liposomes have a significant advantage in reducing early postoperative opioid use. A non-inferior study of bupivacaine liposome and bupivacaine hydrochloride combined with bupivacaine hydrochloride intermuscular brachial plexus block in patients with total shoulder arthroplasty by Neil A Hanson et al. found that although there was a statistically significant reduction in opioid use on day 3 after surgery, However, the cumulative use of opioids in the bupivacaine hydrochloride group within 3 days after surgery did not show significant inferiority.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liu Tianzhu, M.D.; Phone Number: 13098866448; Email: liutzh@126.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Tianzhu Liu
      • Contact: Tianzhu Liu, M.D.; Phone Number: 13098866448; Email: liutzh@126.com
      • Contact: Tianzhu, M.D.; Phone Number: 13098866448; Email: liutzh@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged 18-90 years;
• ASA Class I ~ III;
• Patients undergoing elective median sternotomy.

Exclusion Criteria:

• Emergency surgery;
• Re-operation;
• Coagulation dysfunction;
• Preoperative left ventricular function was poor (ejection fraction <35%);
• Systemic infection or injection site infection;
• Neuromuscular diseases;
• Mental illness;
• Dependence on psychotropic drugs;
• Allergic to bupivacaine liposomes and bupivacaine;
• Patients have participated in previous trials or have been determined by a surgeon or anesthesiologist to be unsuitable for randomization;
• Failure to obtain written informed consent from the patient or his/her representative

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mixture of liposome bupivacaine and bupivacaine hydrochloride; The same anesthesiologist with experience in regional block was used for ultrasound guided bilateral transverse thoracic muscle plane block (T4-5 interstital space, paracentral transverse axis position). According to the literature, in this study, 1.33% bupivacaine liposome 10 mL + 0.5% bupivacaine hydrochloride 10 ml was used.	Procedure: Transverse thoracic muscle plane block (TTMPB) using liposomal bupivacaine and bupivacaine mixture; Liposomal bupivacaine and bupivacaine mixture were used for transverse thoracic muscle plane block (TTMPB) in experimental group.
Active Comparator: Bupivacaine hydrochloride alone; The same anesthesiologist with experience in regional block was used for ultrasound guided bilateral transverse thoracic muscle plane block (T4-5 interstital space, paracentral transverse axis position). According to the literature, in this study, 0.5% bupivacaine 20ml was used.	Procedure: Transverse thoracic muscle plane block (TTMPB) using bupivacaine hydrochloride; Bupivacaine hydrochloride was used for transverse thoracic muscle plane block (TTMPB) in active control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Third-day opioid consumption	Opioid consumption was converted to Milligram morphine equivalent (MME) using the analgesic Drug Equivalence calculator.	48-72 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative opioid consumption 72 hours after surgery	Opioid consumption was converted to Milligram morphine equivalent (MME) using the analgesic Drug Equivalence calculator.	0-72 hours after surgery
Numerical rating scales, NRS	Numerical rating scales, NRS: 0-10 A score of 0 is reported as completely painless, and a score of 10 is reported as the most intolerable pain.	24 hours, 48 hours and 72 hours after surgery
Sensory block resolution time	Time of resolution of numbness in the sternum skin.	0-72 hours after surgery
Consumption of acetaminophen	Acetaminophen requirement after surgery.	0-72 hours after surgery
Consumption of rescue opioid administration	Rescue opioid is administrated if the NRS > 4	0-72 hours after surgery
Patient satisfaction	Patient satisfaction with postoperative pain management. (0-5, 0 is very dissatisfied and 5 is very satisfied)	0-72 hours during and after surgery
Adverse reactions	Adverse reactions related to block procedure.	0-72 hours during and after surgery

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Investigators: Study Director: Mei Wei, M.D., Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2024
• Primary Completion (Actual): October 24, 2024
• Study Completion (Estimated): October 12, 2026

Study Registration Dates

• First Submitted: October 12, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Bupivacaine
• Other Study ID Numbers: Tongji Hospital102114-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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