Liposomal Bupivacaine Versus Continuous Peripheral Nerve Blocks for Analgesia Following Ankle Surgery: A Randomized, Observer and Participant Masked, Active Control, Non-Inferiority Study
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- First postoperative week daily average pain level
研究概览
简要总结
Postoperative pain remains undertreated. Opioids have well-known limitations for both individuals and society, and while single-injection peripheral nerve blocks with unencapsulated local anesthetic provide potent analgesia, their duration is measured in hours while post-surgical pain usually outlasts this duration. Continuous peripheral nerve blocks prolong analgesia but may possibly be replaced with liposomal bupivacaine with a reported duration of up to 72-96 hours (Schwartz. J Clin Anesth 2024). In comparison to continuous peripheral nerve blocks, liposomal bupivacaine eliminates a time-consuming catheter insertion as well as the risks of catheter dislodgement, localized infection, local anesthetic leakage, and infusion pump malfunction. Furthermore, liposomal bupivacaine significantly reduces the burden on both patients and healthcare providers as it does not require the use of a portable infusion pump, local anesthetic reservoir, or perineural catheter to be carried, managed, or eventually removed. Notably, the potential for local anesthetic-induced myotoxicity, and cardiac/neurologic toxicity is reduced or negated altogether. And the cost of liposome bupivacaine is less than the combined cost of a catheter set, insertion equipment, portable infusion pump, large reservoir of local anesthetic, and healthcare provider oversight.
Therefore, should a single injection of liposomal bupivacaine be demonstrated to provide at least non-inferior analgesia and opioid sparing as a continuous peripheral nerve block, it would be a far superior analgesic benefiting patients, providers, hospitals, and payers such as Medicare and private health insurance. Randomized, active-controlled clinical trials are required to compare the newer liposomal bupivacaine to continuous peripheral nerve blocks. The ultimate objective of the proposed research study is to determine if liposomal bupivacaine in a peripheral nerve block is at least non-inferior to a continuous peripheral nerve block following moderate-to-severely painful ankle surgery.
This is a single-center clinical trial. The investigators will randomize participants to either a liposomal bupivacaine combined with unencapsulated bupivacaine single-injection popliteal-sciatic and saphenous nerve block group, or single injections of unencapsulated bupivacaine followed by a continuous popliteal-sciatic bupivacaine infusion.
详细描述
For individuals of childbearing potential, a sample of urine will be collected before any study interventions to confirm a non-pregnant state (this is standard procedure for all surgical patients). Participants will have a peripheral intravenous (IV) catheter inserted, standard noninvasive monitors applied, supplemental oxygen administered via a nasal cannula or face mask and positioned prone. Midazolam and fentanyl (IV) will be titrated for patient comfort, while ensuring that patients remain responsive to verbal cues. The area of insertion on the ipsilateral side as the surgery will be sterilely prepared, and a clear, sterile, fenestrated drape applied.
Treatment group allocation (randomization). Participants will be randomized and allocated to one of two possible treatments groups by the investigational pharmacist based on computer-generated lists in a 1:1 ratio stratified by treatment center and surgical procedure in blocks of 4. All study medication will be prepared and provided by the Investigational Drug Service and the syringes never shown to the participants or surgeons to retain masking (liposomal bupivacaine is white while unencapsulated bupivacaine is clear).
Treatment groups:
- Experimental (includes liposomal bupivacaine)
- Standard-of-Care (control)
Popliteal-sciatic nerve block. The sciatic nerve bifurcation will be identified by ultrasound in the short-axis view. The bifurcation will be defined as the most proximal point at which the tibial and common peroneal nerves have separated. Using ultrasound guidance, a standard Tuohy block needle will be advanced through a skin wheal of lidocaine until its tip is in the hypoechoic area immediately distal to the sciatic nerve bifurcation where the 2 branches of the sciatic nerve are adjacent but distinct deep to the paraneurium between the epineurium and paraneurium (the "subparaneural space/compartment"). Twenty milliliters of study fluid will be injected in divided doses with repeated negative aspiration. The study fluid will be comprised of:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
All individuals will be masked to treatment group assignment with the exception of the investigational pharmacists who prepare the study medication and the investigators who are administering the single-injection peripheral nerve blocks and inserting the perineurial catheter.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients of at least 18 years of age
- •Undergoing a primary, unilateral, moderate-to-severely painful ankle surgery
- •Planned single-injection adductor canal nerve block and popliteal-sciatic catheter
- •Weight > 50 kg (to minimize the risk of local anesthetic toxicity)
排除标准
- •chronic opioid or tramadol use: daily oxycodone equivalents > 20 mg for > 4 weeks
- •neuro-muscular deficit of the surgical limb
- •moderate pain (NRS > 3) in an anatomic location other than the surgical site
- •surgery outside the sciatic and saphenous nerve distributions
- •history of opioid misuse
- •inability to communicate with the investigators
- •inability to contact the investigators during the treatment period, and vice versa (e.g., lack of telephone access)
- •incarceration
- •allergy to amide local anesthetics or other study medication
- •active lower extremity infection or other contraindications to a peripheral nerve catheter
研究组 & 干预措施
Liposomal Bupivacaine (Experimental)
Popliteal-sciatic nerve block: 10 mL of unencapsulated bupivacaine 0.375% and 10 mL of liposomal bupivacaine 1.33% (Exparel, Pacira BioSciences, Tampa, Florida) admixed within a 20 mL syringe.
Adductor canal (saphenous) nerve block: 10 mL of unencapsulated bupivacaine 0.375% and 10 mL of liposomal bupivacaine 1.33% (Exparel, Pacira BioSciences, Tampa, Florida) admixed within a 20 mL syringe.
Postoperative perineural infusion: Basal rate 5 mL/h; patient-controlled bolus of 4 mL; 30 minute lockout; and reservoir with normal saline (500 mL).
干预措施: Popliteal nerve block including liposomal bupivacaine (Drug)
Liposomal Bupivacaine (Experimental)
Popliteal-sciatic nerve block: 10 mL of unencapsulated bupivacaine 0.375% and 10 mL of liposomal bupivacaine 1.33% (Exparel, Pacira BioSciences, Tampa, Florida) admixed within a 20 mL syringe.
Adductor canal (saphenous) nerve block: 10 mL of unencapsulated bupivacaine 0.375% and 10 mL of liposomal bupivacaine 1.33% (Exparel, Pacira BioSciences, Tampa, Florida) admixed within a 20 mL syringe.
Postoperative perineural infusion: Basal rate 5 mL/h; patient-controlled bolus of 4 mL; 30 minute lockout; and reservoir with normal saline (500 mL).
干预措施: Adductor canal nerve block including liposomal bupivacaine (Drug)
Liposomal Bupivacaine (Experimental)
Popliteal-sciatic nerve block: 10 mL of unencapsulated bupivacaine 0.375% and 10 mL of liposomal bupivacaine 1.33% (Exparel, Pacira BioSciences, Tampa, Florida) admixed within a 20 mL syringe.
Adductor canal (saphenous) nerve block: 10 mL of unencapsulated bupivacaine 0.375% and 10 mL of liposomal bupivacaine 1.33% (Exparel, Pacira BioSciences, Tampa, Florida) admixed within a 20 mL syringe.
Postoperative perineural infusion: Basal rate 5 mL/h; patient-controlled bolus of 4 mL; 30 minute lockout; and reservoir with normal saline (500 mL).
干预措施: Continuous popliteal nerve block with normal saline (Drug)
Unencapsulated Bupivacaine (Control)
Popliteal-sciatic nerve block: 20 mL of unencapsulated bupivacaine 0.375% with epinephrine (1:400,000) within a 20 mL syringe.
Adductor canal (saphenous) nerve block: Standard-of-Care Group: 20 mL of unencapsulated bupivacaine 0.375% with epinephrine (1:400,000) within a 20 mL syringe.
Postoperative perineural infusion: Basal rate 5 mL/h; patient-controlled bolus of 4 mL; 30 minute lockout; and reservoir of unencapsulated bupivacaine 0.125% (500 mL).
干预措施: Popliteal nerve block with exclusively unencapsulated bupivacaine (Drug)
Unencapsulated Bupivacaine (Control)
Popliteal-sciatic nerve block: 20 mL of unencapsulated bupivacaine 0.375% with epinephrine (1:400,000) within a 20 mL syringe.
Adductor canal (saphenous) nerve block: Standard-of-Care Group: 20 mL of unencapsulated bupivacaine 0.375% with epinephrine (1:400,000) within a 20 mL syringe.
Postoperative perineural infusion: Basal rate 5 mL/h; patient-controlled bolus of 4 mL; 30 minute lockout; and reservoir of unencapsulated bupivacaine 0.125% (500 mL).
干预措施: Adductor canal nerve block with exclusively unencapsulated bupivacaine (Drug)
Unencapsulated Bupivacaine (Control)
Popliteal-sciatic nerve block: 20 mL of unencapsulated bupivacaine 0.375% with epinephrine (1:400,000) within a 20 mL syringe.
Adductor canal (saphenous) nerve block: Standard-of-Care Group: 20 mL of unencapsulated bupivacaine 0.375% with epinephrine (1:400,000) within a 20 mL syringe.
Postoperative perineural infusion: Basal rate 5 mL/h; patient-controlled bolus of 4 mL; 30 minute lockout; and reservoir of unencapsulated bupivacaine 0.125% (500 mL).
干预措施: Continuous popliteal nerve block with unencapsulated bupivacaine (Drug)
结局指标
主要结局
First postoperative week daily average pain level
时间窗: Postoperative days 1-7
The NRS is a highly-sensitive measure of pain intensity with numbers ranging from 0 to 10, zero equivalent to no pain and 10 equivalent to the worst imaginable pain. The primary outcome measure will be a combination of daily "average" NRS and opioid consumption in oxycodone equivalents. In order to claim that liposomal bupivacaine is non-inferior to a perineural bupivacaine infusion for each postoperative day, both NRS and opioid consumption must be at least non-inferior for that day. We will use a stepwise gatekeeping statistical procedure beginning on Day 1 and progressing daily through Day 7. Using this statistical method, no adjustment in alpha will be necessary to control Type 1 error through all 7 days.
First postoperative week cumulative opioid consumption
时间窗: Postoperative days 1-7
Cumulative opioid consumption from recovery room discharge through postoperative day 7 measured in oxycodone equivalents. The primary outcome measure will be a combination of daily "average" NRS and opioid consumption in oxycodone equivalents. In order to claim that liposomal bupivacaine is non-inferior to a perineural bupivacaine infusion for each postoperative day, both NRS and opioid consumption must be at least non-inferior for that day. We will use a stepwise gatekeeping statistical procedure beginning on Day 1 and progressing daily through Day 7. Using this statistical method, no adjustment in alpha will be necessary to control Type 1 error through all 7 days.
次要结局
- Daily worst/maximum pain(Collected daily postoperative days 1-7)
- Daily "average" pain(Collected daily postoperative days 1-7)
- Daily lowest/minimal pain(Collected daily postoperative days 1-3)
- Daily "current" pain(Collected daily postoperative days 1-3)
- Daily opioid consumption(Collected daily postoperative days 1-7)
- Brief Pain Inventory, short form (Interference Subscale)(Collected daily postoperative days 1-3)
- Awakenings due to pain(Collected daily postoperative days 1-7)
- Days hospitalized(Postoperative days 0-7)
研究者
Brian M. Ilfeld, MD, MS
Professor of Anesthesiology, In Residence
University of California, San Diego