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

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

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.

Study Overview

• Status: Completed
• Conditions: Total Knee Arthroplasty
• Intervention / Treatment: Drug: Peripheral nerve blocks with Bupivacaine; Drug: Intra articular injection with Ropivacaine; Drug: Intra articular injection with liposomal bupivacaine

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients with an American Society of Anesthesiologists (ASA) physiological status I-III
2. Patients presenting for unilateral primary total knee replacement.
3. No focal neurologic deficit of the surgical lower extremity.
4. Cognitively intact with the ability to sign informed consent

Exclusion Criteria:

1. Chronic pain syndromes such as fibromyalgia or complex regional pain syndrome
2. History of long term use of daily opioids (>1 months) with oral morphine equivalent (OME) >5mg/day.
3. Body mass index (BMI) > 40 kg/m2
4. Allergies to medications used in this study such as: fentanyl, hydromorphone, ketorolac, ibuprofen, acetaminophen, local anesthetics, oxycodone, OxyContin, tramadol, ondansetron, droperidol, or dexamethasone, celecoxib

5. 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.
6. Impaired cognitive function or inability to understand the study protocol
7. 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.).
8. Previous contralateral knee replacement managed with regional or periarticular injection
9. Unable to follow-up at the 3 month interval at Mayo Clinic in Rochester, Minnesota
10. Pregnancy or breast feeding (women of child-bearing potential, must have a negative pregnancy test)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Peripheral Nerve Block (PNB); 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; 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.; Other Names: Marcaine; Sensorcaine
Active Comparator: Ropivacaine (PAI-R); 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; 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.; Other Names: Naropin
Active Comparator: Liposomal Bupivacaine (PAI-L); 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; 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.; Other Names: Exparel

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Sandra Kopp, MD, Mayo Clinic

Publications and helpful links

General Publications

• Amundson AW, Johnson RL, Abdel MP, Mantilla CB, Panchamia JK, Taunton MJ, Kralovec ME, Hebl JR, Schroeder DR, Pagnano MW, Kopp SL. A Three-arm Randomized Clinical Trial Comparing Continuous Femoral Plus Single-injection Sciatic Peripheral Nerve Blocks versus Periarticular Injection with Ropivacaine or Liposomal Bupivacaine for Patients Undergoing Total Knee Arthroplasty. Anesthesiology. 2017 Jun;126(6):1139-1150. doi: 10.1097/ALN.0000000000001586.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: July 29, 2014
• First Submitted That Met QC Criteria: August 21, 2014
• First Posted (Estimate): August 22, 2014

Study Record Updates

• Last Update Posted (Actual): August 31, 2017
• Last Update Submitted That Met QC Criteria: August 29, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine; Ropivacaine
• Other Study ID Numbers: 14-002083

Plan for Individual participant data (IPD)

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