Peripheral Nerve Blocks vs Periarticular Local Anesthetic Injection for Total Knee Arthroplasty (TKA)

Study Overview
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Brief Summary
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The purpose of this study is to find a better way to make patients comfortable after their knee surgery. The investigators compared three ways of providing pain relief, either by use of a nerve block at the femoral and sciatic nerve areas, or with actual injections in the surgical joint area with one of two different medicines, either ropivacaine or liposomal bupivacaine (Exparel®). The hypothesis was that the nerve block at the femoral and sciatic nerve areas would result in lower pain scores and opioid consumption than either of the two injections in the surgical joint area.

Official Title
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Prospective, Randomized, Controlled Trial Comparing Continuous Femoral and Single Injection Sciatic Peripheral Nerve Blocks vs Periarticular Injection With Ropivacaine or Liposomal Bupivacaine (Exparel) on Patients Undergoing Total Knee Arthroplasty

Conditions
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Total Knee Arthroplasty

Intervention / Treatment
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* Drug: Peripheral nerve blocks with Bupivacaine
* Drug: Intra articular injection with Ropivacaine
* Drug: Intra articular injection with liposomal bupivacaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with an American Society of Anesthesiologists (ASA) physiological status I-III Patients presenting for unilateral primary total knee replacement. No focal neurologic deficit of the surgical lower extremity. Cognitively intact with the ability to sign informed consent Exclusion Criteria: Chronic pain syndromes such as fibromyalgia or complex regional pain syndrome History of long term use of daily opioids (>1 months) with oral morphine equivalent (OME) >5mg/day. Body mass index (BMI) > 40 kg/m2 Allergies to medications used in this study such as: fentanyl, hydromorphone, ketorolac, ibuprofen, acetaminophen, local anesthetics, oxycodone, OxyContin, tramadol, ondansetron, droperidol, or dexamethasone, celecoxib Major systemic medical problems such as: Severe renal disorder defined as glomerular filtration rate (GFR) <50 units/m2 Cardiovascular disorders defined as congestive heart failure (CHF) New York Heart Association (NYHA) class III-IV Severe hepatic disorder defined as current or past diagnosis of acute/subacute necrosis liver, acute hepatic failure, chronic liver disease, cirrhosis (primary biliary cirrhosis), fatty liver, chronic hepatitis/toxic hepatitis, liver abscess, hepatic coma, hepatorenal syndrome, other disorders of liver. Impaired cognitive function or inability to understand the study protocol Contraindication to a regional anesthesia technique (e.g., preexisting neuropathy in the operative extremity, coagulopathy [platelets < 100,000, International Normalized Ratio (INR) >1.5], refusal, etc.). Previous contralateral knee replacement managed with regional or periarticular injection Unable to follow-up at the 3 month interval at Mayo Clinic in Rochester, Minnesota Pregnancy or breast feeding (women of child-bearing potential, must have a negative pregnancy test)

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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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Peripheral Nerve Block (PNB)<br>This group received a continuous femoral nerve block and a single injection sciatic nerve block consisting of the following: Peripheral nerve blocks with Bupivacaine. | Drug: Peripheral nerve blocks with Bupivacaine<br>* Subjects received Bupivacaine 0.5% preoperatively, then Bupivacaine 0.2% upon post anesthesia care unit (PACU) arrival via femoral nerve block, then Bupivacaine 0.25% via single-injection sciatic nerve.<br>* Other names: Sensorcaine;|
| Active Comparator: Ropivacaine (PAI-R)<br>This group received intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure. | Drug: Intra articular injection with Ropivacaine<br>* Subjects received an intra articular injection with Ropivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Ropivacaine dose depended upon body weight: 50-74.9 kg: 200 mg, 75-99.9 kg: 300 mg, 100-125 kg: 400 mg.<br>* Other names: Naropin;|
| Active Comparator: Liposomal Bupivacaine (PAI-L)<br>This group received Intra articular injection with liposomal bupivacaine, a total volume of 120 milliliters (mL) injected in the periarticular structures by the surgeon. Following the current, standardized practice for periarticular infiltration, approximately 30 - 40 mL of solution was injected into the posterior capsule just prior to cementing the implants in place and 40 - 50 mL of solution injected into the medial and lateral retinaculum while the cement was hardening and prior to deflation of the tourniquet. The remaining volume of approximately 40 mL was injected into the quadriceps tendon and subcutaneous tissue prior to skin closure. | Drug: Intra articular injection with liposomal bupivacaine<br>* Subjects received an intra articular injection with liposomal bupivacaine, a total volume of 120 mL injected in the periarticular structures by the surgeon. Patients weighing 50-125 kg received 266mg of Liposomal Bupivacaine.<br>* Other names: Exparel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Pain Post-Operative Day (POD) 1 (Morning) | Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable. | Post-Operative Day 1, approximately 6 am to 12:00 pm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Pain Post-Postanesthesia Care Unit (PACU) | Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable. | Post-operative Day 0, approximately 12 pm to 12 am | 
| Maximum Pain Post-PACU | Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable. | Post-operative Day 0, approximately 12 pm to 12 am | 
| Average Pain POD 1 (24 Hours) | Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable. | POD 1, approximately 12 am to 12 am next day | 
| Maximum Pain POD 1 (24 Hours) | Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable. | POD 1, approximately 12 am to 12 am next day | 
| Average Pain POD 2 (24 Hours) | Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable. | POD 2, approximately 12 am to 12 am next day | 
| Maximum Pain POD 2 (24 Hours) | Pain was measured on a 1-10 numeric pain rating scale (NRS) with 0=no pain, and 10=worst pain imaginable. | POD 2, approximately 12 am to 12 am next day | 
| Preoperative Daily Opioid Use | Opioid consumption will be documented in the patient electronic medical record by the nursing staff caring for the patient. | baseline | 
| Intraoperative Opioid Use | Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient. | During the procedure, approximately 2 hours after start of the procedure | 
| PACU Opioid Use | Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient. | Approximately 2 hours after entry in PACU | 
| POD 0 Post-PACU Opioid Use | Additional opioid medications that were taken by subjects (recorded at the same time as the time points for measuring pain). Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient. | POD 0, approximately 12 pm to 12 am | 
| POD 1 Opioid Use | Additional opioid medications that were taken by subjects (recorded at the same time as the time points for measuring pain). Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient. | POD 1, approximately 12 am to 12 am next day | 
| POD 2 Opioid Use | Additional opioid medications that were taken by subjects (recorded at the same time as the time points for measuring pain). Opioid consumption was documented in the patient electronic medical record by the nursing staff caring for the patient. | POD 2, approximately 12 am to 12 am next day | 
| Hospital Length of Stay | The hospital length of stay was measured from the date of admittance until the date of discharge. | Approximately 3 days | 
| Balance Testing on Operative Leg Using Unipedal Stance Time | In order to measure clinical balance, unipedal stance time (UST) was collected as an indicator of balance and fall risk. Timing (in seconds) began upon withdrawal of support and continued until the uplifted foot returned to the floor, the subject required support, or if the subject reached a time limit of 30 seconds. The best performance of three repetitions was recorded for analysis. Normative values for the UST are available. A UST threshold of 30 seconds yields a sensitivity of 95% and a specificity of 58% in identifying those with a history of falls. The first five seconds of unipedal stance is indicative of dynamic balance; inability to maintain unipedal stance for five seconds is a significant predictor of injurious falls. | baseline, approximately 12 weeks |