Exparel vs. Marcaine ESP Block for Post-cardiac Surgical Pain

Study Overview
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Brief Summary
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The goal of this pilot study is to describe and compare Ultrasound-Guided Erector Spinae Plane (ESP) Blocks using Exparel® (bupivacaine liposome injectable suspension) to Marcaine® (bupivacaine hydrochloride) for pain management and outcomes after cardiac surgeries.

Detailed Description
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Postoperative pain is a major concern for patients after cardiovascular surgery. With an increasing emphasis on improving perioperative care arising from evidence-based protocols such as Enhanced Recovery After Surgery (ERAS), reducing postoperative pain not only increases patient satisfaction, but also decreases postoperative complications and improves outcomes. Reduced postoperative pain also decreases rates of pneumonia and time on mechanical ventilation, in the ICU, or in the hospital. Importantly, decreasing postoperative pain can also reduce high dose opioid usage, the established method of managing postoperative pain, thereby decreasing rates of nausea/vomiting, intubation time, and mortality. Methods of reducing postoperative pain, such as neuraxial anesthesia and deep plexus blocks, are associated with an increased risk of epidural hematoma; an alternate solution, therefore, is using fascial plane blocks. Since 2018, our institution is one of very few that uses pre-operative fascial plane blocks for cardiac surgery patients, implementing bilateral plane blocks for the sternotomy approach and unilateral plane blocks for the right mini-thoracotomy approach. Results from these blocks have been quite favorable but not yet validated. It would be unethical to do a study in which subjects are randomized to not receive the block preoperatively. Therefore, this study is designed to better understand the overall effects of these blocks by comparing FDA approved medications, Exparel (current practice at RWJUH) and Marcaine. Marcaine (0.25% bupivacaine HCl) has an onset of action on the order of seconds and generally within one minute from the time of injection, and an effect duration of roughly seven hours. Exparel is a commercially available extended-release formulation of liposomal bupivacaine, which extends the effect duration to an upward of 72 hours from the time of injection with similarly immediate onset of action. Several studies have compared local injections of Marcaine (plain bupivacaine) with Exparel (liposomal bupivacaine) in the setting of inguinal hernia repair, knee arthroplasty, breast augmentation, and hemorrhoidectomy, with results favoring the use of liposomal bupivacaine based on improvements in subjective pain at the initial postoperative pain assessment.(6) Clinical trials are currently underway, investigating the effect of liposomal bupivacaine for local anesthesia and compared with epidural anesthesia in thoracoscopic surgery. In a recent clinical trial published in the Journal of the American Medical Association (JAMA), patients undergoing cardiothoracic or vascular surgery subjected to truncal incisions did not demonstrate a significant benefit with respect to pain control or adjunctive opioid usage when treated with liposomal bupivacaine over plain bupivacaine via local injection. Still, a gap in the literature exists with respect to the use of liposomal bupivacaine versus plain bupivacaine for erector spinae plane block in the setting of sternotomy. The aim of this prospective study is to determine the impact of preoperative fascial plane blocks with Exparel compared to Marcaine on outcomes following cardiac procedures.

Official Title
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Randomized Control Trial to Assess the Efficacy of Preoperative Erector Spinae Blocks on Cardiac Surgery Postoperative Outcomes

Conditions
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Pain, Postoperative, Opioid Use, Perioperative Complication, Heart Diseases

Intervention / Treatment
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* Drug: bupivacaine liposome injectable suspension
* Drug: Bupivacaine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (18 years-no upper age limit) Scheduled for mini thoracotomy (i.e. valve repair) or open sternotomy (i.e. bypass graft) at single academic medical center (in and out-patients). Exclusion Criteria: Patients will be excluded if they: Are currently on pain medication or pain regimen Convert to open heart procedure (for thoracotomies) Require additional procedure then originally scheduled Undergo emergent surgery Are non-English speaking (The majority of the PI's patient population speak English. As a pilot study we cannot afford the time, effort or money to enroll non-English speaking subjects.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exparel<br>The experimental medication (Exparel) will be administered per standard of care via ultrasound-guided erector spinae plane (ESP) blocks, bilaterally for sternotomy and unilaterally for mini-thoracotomy. The drug will be administered prior to cardiac surgery. The dosage will be determined by patient body weight. For this pilot project we anticipate consenting 120 subjects to obtain 96 evaluable subjects; 48 Mini thoractomies (N=24 Exparel, N=24 Marcaine) 48 Open sternotomies (N=24 Exparel, N=24 Marcaine). | Drug: bupivacaine liposome injectable suspension<br>* Bupivacaine liposome injectable suspension (Exparel) will be administered by ultrasound-guided ESP block, unilaterally if thoracotomy on ipsilateral side, bilaterally if median sternotomy.<br>* Other names: Exparel;|
| Active Comparator: Marcaine<br>The active comparator medication (Marcaine) will be administered per standard of care via ultrasound-guided erector spinae plane (ESP) blocks, bilaterally for sternotomy and unilaterally for mini-thoracotomy. The drug will be administered prior to cardiac surgery. The dosage will be determined by patient body weight. For this pilot project we anticipate consenting 120 subjects to obtain 96 evaluable subjects; 48 Mini thoracotomies (N=24 Exparel, N=24 Marcaine) 48 Open sternotomies (N=24 Exparel, N=24 Marcaine). | Drug: Bupivacaine Hydrochloride<br>* Bupivacaine HCl (Marcaine) will be administered by ultrasound-guided ESP block, unilaterally if thoracotomy on ipsilateral side, bilaterally if median sternotomy.<br>* Other names: Marcaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative opioid consumption | Postoperative opioid consumption within first five postoperative days, reported as average mg/day in morphine equivalents. | Postoperative days 0 through 5 | 
| Postoperative nonopioid analgesic consumption | Postoperative non-opioid analgesic (Pregabalin, Gabapentin, selective serotonin reuptake inhibitor (SSRI), selective norepinephrine reuptake inhibitor (SNRI), Ketorolac, Tramadol, Ibuprofen, and Acetaminophen) consumption within first five postoperative days, reported as average mg/day in morphine equivalents. | Postoperative days 0 through 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inpatient postoperative pain score | Pain scores through postoperative day five, using the standard Numeric Rating Scale (NRS), wherein a score of 0 corresponds to no pain, 5 to moderate pain, and 10 to worst possible pain, reported as mean score over all five days. | Postoperative days 0 through 5 | 
| Outpatient postoperative pain score | Single pain score at follow-up visit, using the standard Numeric Rating Scale (NRS), wherein a score of 0 corresponds to no pain, 5 to moderate pain, and 10 to worst possible pain. | Obtained within 30 days following surgery | 
| 30-day mortality rate | Proportion of patients who expire within 30 postoperative days from the index operation. | Through postoperative day 30 | 
| 30-day major morbidity rate | Proportion of patients who experience the composite outcome of major morbidity, defined as the occurrence of any of the following within 30 postoperative days from the index operation: pneumonia, respiratory failure with ventilatory support >48h, pulmonary embolism (PE), deep vein thrombosis (DVT), multi-organ dysfunction syndrome, postoperative myocardial infarction (MI), renal replacement therapy, infection of wound or line, readmission, sustained postoperative atrial or ventricular arrhythmia, new postoperative atrial fibrillation, exacerbation of pre-existing atrial fibrillation | Through postoperative day 30 | 
| Postoperative qualify of life | Measured as change on the 12-item Short Form Survey (SF-12) from preoperative baseline to followup. Scores on the SF-12 range from 0 to 100, with higher scores indicating better physical and mental health. | Within the range of 30 days prior to surgery to 30 days after surgery | 
| Hospitalization cost | Before-insurance cost of hospitalization and treatment. | Study duration, limited to one year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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plane block, sternotomy, thoracotomy, surgery, postoperative, cardiac, pain, anesthesia, opioid, pragmatic trial