Liposomal Bupivacaine Versus Plain Bupivacaine After Intercostal Injections For Pain Management After Thoracoscopy
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|ClinicalTrials.gov Identifier: NCT03737292|
Recruitment Status : Suspended (Temporarily suspended due to Pandemic.)
First Posted : November 9, 2018
Last Update Posted : April 15, 2020
The purpose of this study is to assess pharmacokinetics of liposomal bupivacaine (Exparel) after multilevel intercostal injections of this local anesthetic for pain control during and after thoracoscopic surgeries.
The specific aim of this study is to evaluate plasma concentration of bupivacaine after intraoperative intercostal injections of 266 mg of liposomal bupivacaine and compare it to plasma concentrations of bupivacaine after intercostal injections of 2mg/kg of 0.5% plain Bupivacaine with maximal dose of 30 ml or 150 mg.
The hypothesis of the study is that plasma concentration of bupivacaine after intercostal injections of 266 mg of liposomal bupivacaine will be similar to concentrations after injections of plain bupivacaine, and will remain below the toxic level threshold range of 2000-3000 ng/mL (2-3 mg/L) at which central nervous system and cardiovascular adverse events would be expected to occur.
The secondary objective is to evaluate if intercostal injections of 266 mg of liposomal bupivacaine will significantly reduce opioid consumption and postsurgical pain, within the first 48 hours and up to 3 months after minimally invasive thoracic surgeries, to determine if both acute and chronic post-thoracotomy pain can be decreased by intraoperative intercostal injections of liposomal bupivacaine.
Additionally, the rate of pneumonia, the rate of atrial fibrillation and length of hospital stay will be assessed as secondary outcomes after thoracic surgeries. These outcomes can be affected by the level of postoperative pain and inflammation.
Significance of this study: If positive, the results of this research have the potential to significantly improve pain management after thoracoscopic surgery.
Based on prior experience, prolonged analgesia after liposomal bupivacaine injection is safe, and may help reduce perioperative opioid consumption and decrease opioid related complications. It will improve patient comfort, eliminate need for indwelling neuraxial catheters and risks associated with them.
|Condition or disease||Intervention/treatment||Phase|
|Pain, Postoperative Pharmacokinetics||Drug: Exparel Drug: Bupivacaine||Phase 4|
Liposomal bupivacaine is a relatively new drug formulation. Its safety and side effect profile after intercostal injection has not been extensively studied. Most of the data comes from studies where the medicine was used for wound infiltrations and peripheral nerve blocks for orthopedic surgeries, or from preclinical volunteer studies. PK profile of Exparel varies significantly with different blocks and administration techniques. Very few data are available about pharmacokinetics of the drug after intercostal injections.
Because Exparel contains plain bupivacaine in a liposomal form, it allows for a slower release of the medication from the injection site into the blood stream, and prolongs the duration of action of this local anesthetic. During intercostal infiltration, a local anesthetic is injected into a highly vascular area with increased rate of intravascular absorption and potential risk of toxicity.
Also, because liposomal formulation provides a slow release of local anesthetic, the maximum recommended dose of Exparel (266mg) for intercostal injections is higher than a maximum recommended dose for plain bupivacaine (150mg), which can theoretically increase the risk of local anesthetic toxicity.
The plan of this s to analyze a pharmacokinetic profile and safety of liposomal bupivacaine compared with plain bupivacaine HCl. it is understood that absolute numbers can differ because the doses of the two formulations are different. Unfortunately, the dose of plain bupivacaine cannot be increased to match the dose of Exparel because of the risk of toxicity. The dose of Exparel should not be lowered, because lower doses have been shown to be less effective and are not clinically used at Hershey Medical Center.
Based on prior experience, it is known that prolonged analgesia after Exparel injection is safe, and can help reduce perioperative opioid consumption and decrease opioid related complications.
The goal of this study is to demonstrate that despite the higher total dose of bupivacaine administered via Exparel formulation as an intercostal injection, maximal plasma concentration will remain within therapeutic levels of 700-1,000 ng/mL, and below toxic level threshold range of 2000-3000 ng/mL at which central nervous system and cardiovascular adverse events would be expected to occur. As a result, many more patients in the future can benefit from a wider use of Exparel for pain management after thoracic surgeries.
Pneumonia and atrial fibrillation are well known complications of thoracic surgeries. The etiology of atrial fibrillation after lung resection involves a combination of postoperative hyperadrenergic activity and atrial dilatation. Increased vagal tone, atrial inflammation, pulmonary hypertension, hypoxemia, or infection may also contribute. Preclinical studies have shown a multitude of interactions between local anesthetics and the inflammatory system. It is known that proinflammatory effects are attenuated by perioperative intravenous lidocaine infusion via blocking the process of priming of polymorphonuclear granulocytes (PMN). Since pneumonia and atrial fibrillation after thoracic surgery can be attributed in part to inflammation, the hypothesis is that liposomal bupivacaine, due to higher concentration and longer duration of action, can decrease incidence of these complications and improve hospital length of stay.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This is a prospective randomized controlled, double blind study.|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Comparison of Plasma Concentration And Efficacy Of Liposomal Bupivacaine And Plain Bupivacaine After Intercostal Injections For Pain Management After Thoracoscopy|
|Actual Study Start Date :||April 9, 2019|
|Estimated Primary Completion Date :||March 2021|
|Estimated Study Completion Date :||June 2021|
Intercostal injection of 266mg of Exparel diluted to 30 ml.
The intercostal blocks will be performed at several levels corresponding to the incisions and chest tube insertion sites + two levels above and two levels below the incisions. On average, 5-6 intercostal spaces will be injected with 4-5 ml of local anesthetic at each level.
Active Comparator: Bupivacaine
Intercostal injection of 0.5% Bupivacaine 2 mg/kg dose diluted to 30 ml.
The intercostal injections of 0.5% Bupivacaine 2 mg/kg dose diluted to 30 ml total will be performed at several levels corresponding to the incisions and chest tube insertion sites + two levels above and two levels below the incisions.
- Plasma concentration of bupivacaine [ Time Frame: 0.5, 1, 2, 4, 8, 12, 24, 32, 48, 72 hours after intraoperative multiple level intercostal injections. ]The primary end points to be measured in the study are plasma concentrations of bupivacaine 0.5, 1, 2, 4, 8, 12, 24, 32, 48 hours after intraoperative multiple level intercostal injections of plain Bupivacaine or Exparel. If the patient remains in the hospital, additional samples will be collected at 72 hours. If the patient gets discharged before this time, the last sample will be drawn at time of discharge from the hospital.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03737292
|United States, Pennsylvania|
|Milton S. Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033|
|Principal Investigator:||Zoulfira Nisnevitch-Savarese, MD||Penn State Hershey College of Medicine|