Arthroplasty, Replacement, Knee
Conditions
Keywords
Knee Arthroplasty, Total, Liposomal Bupivicaine
Brief summary
This study seeks to determine whether a new sustained-release local anesthetic solution (Exparel - Liposomal Bupivacaine) injected into the soft tissues around the joint after surgery will decrease opioid consumption and adverse events in opioid-tolerant patients presenting for total knee arthroplasty. The research hypothesis is that the Exparel (study) group will use less opioid in the first 48 hours post-operatively than the control group.
Detailed description
Opioids have been prescribed with increasing frequency for non-acute, non-cancer pain in the last 15 years. Because of this, opioid tolerance in the general population has grown markedly, and opioid tolerant patients can be especially difficult to manage in the perioperative period. In general, they require much higher doses of opioids to obtain similar levels of pain-control compared to opioid-naïve patients and are susceptible to respiratory depression and other adverse events. This study seeks to determine whether a new sustained-release local anesthetic solution (Exparel - Liposomal Bupivacaine) injected into the soft tissues around the joint after surgery will decrease opioid consumption and adverse events in opioid-tolerant patients presenting for total knee arthroplasty.
Interventions
DRUG(Bupivacaine Liposome Injectable Suspension)
Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.
A standard joint injection of 100ml (Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml) will be injected into the soft tissues around the joint after surgery.
Sponsors
University of California, Irvine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and Females age 18+ years old having total knee arthroplasty at UCI * Meet at least one of the following criteria opioid tolerant: * Taking 50mg oral morphine equivalent or more per day * On long-acting opioids (fentanyl pathc, oxycontin, methadone, etc.) * Being followed by a chronic pain physician * All subjects must be free of renal or hepatic dysfunction; defined as: * Glomerular filtration rate \>60 mL/min/1.73m\^2 * AST & ALT \<150, total bilirubin \<1.0, INR \<1.3 (if not taking anticoagulants) * No active hepatitis, no jaundice Control group- received standard periarticular injection Research group- receives Exparel injection
Exclusion criteria
* Allergy to local Anesthetic * Pregnancy * Nursing mothers * Children\<18 years of age * Renal impairment (GFR\<60 mL/min/1.73 m\^2 * Hepatic impairment (active hepatitis, elevated AST or ALT, jaundice) * Any history of ventricular arrhythmia or supraventricular tachycardia, or myocardial infarction within the last six months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 48 Hour Post-surgical Opioid Use | 48 hours | A comparison of group means between the control group and study group with regards to 48 hour opioid use. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recovery Room Opioid Use | Up to 48 hours | Post anesthesia care unit (recovery room) opioid use in total mg morphine IV equivalent in comparison of standard knee injection post-operatively. |
| Average Daily Opioid Use During Admission | Up to 48 hours | Opioid use will be monitored daily from the time of admission in comparison of standard knee injection post-operatively. |
| Average Daily Patient Pain Score | Up to 48 hours | Examining the average daily patient pain score in comparison of standard knee injection post-operatively. The measure is the Visual-Analog-Scale (VAS) for subjective pain reporting. The minimum 0 (no pain) and the maximum is 10 (worst pain imagineable). There is only one measure in the scale (i.e. there are no subscales). Lower scores on the VAS scale equate to less pain and are therefore desirable. |
| Post-operative Complications | Up to 1 month | Examining the post-operative complication in comparison of standard knee injection post-operatively. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EXPAREL® Bupivacaine Liposome Suspension Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours.
(Bupivacaine Liposome Injectable Suspension): Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery. | 20 |
| Standard Periarticular Joint Injection A standard joint injection of 100ml which contains Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml will be injected into the soft tissues around the joint after surgery. | 18 |
| Total | 38 |
Baseline characteristics
| Characteristic | EXPAREL® Bupivacaine Liposome Suspension | Standard Periarticular Joint Injection | Total |
|---|---|---|---|
| Age, Continuous | 64.14 years STANDARD_DEVIATION 10.18 | 60 years STANDARD_DEVIATION 12.83 | 60 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 9 Participants | 12 Participants | 21 Participants |
| Sex: Female, Male Male | 11 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 20 |
| serious Total, serious adverse events | 0 / 18 | 0 / 20 |
Outcome results
Primary
48 Hour Post-surgical Opioid Use
A comparison of group means between the control group and study group with regards to 48 hour opioid use.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EXPAREL® Bupivacaine Liposome Suspension | 48 Hour Post-surgical Opioid Use | 5.32 morphine equivalents | Standard Deviation 1.72 |
| Standard Periarticular Joint Injection | 48 Hour Post-surgical Opioid Use | 5.07 morphine equivalents | Standard Deviation 2.05 |
Secondary
Average Daily Opioid Use During Admission
Opioid use will be monitored daily from the time of admission in comparison of standard knee injection post-operatively.
Time frame: Up to 48 hours
Population: The vast majority of the patients had been discharged by 72 hours post-op, making this outcome low-powered and not useful. Because of this we used the 48 hour pain measurement.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| EXPAREL® Bupivacaine Liposome Suspension | Average Daily Opioid Use During Admission | 100 Total Morphine Equivalents |
| Standard Periarticular Joint Injection | Average Daily Opioid Use During Admission | 103 Total Morphine Equivalents |
Secondary
Average Daily Patient Pain Score
Examining the average daily patient pain score in comparison of standard knee injection post-operatively. The measure is the Visual-Analog-Scale (VAS) for subjective pain reporting. The minimum 0 (no pain) and the maximum is 10 (worst pain imagineable). There is only one measure in the scale (i.e. there are no subscales). Lower scores on the VAS scale equate to less pain and are therefore desirable.
Time frame: Up to 48 hours
Population: The vast majority of the patients had been discharged by 72 hours post-op, making this outcome low-powered and not useful. Because of this we used the 48 hour pain measurement.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| EXPAREL® Bupivacaine Liposome Suspension | Average Daily Patient Pain Score | 4.75 Visual Analog Scale Rating |
| Standard Periarticular Joint Injection | Average Daily Patient Pain Score | 5.75 Visual Analog Scale Rating |
Secondary
Post-operative Complications
Examining the post-operative complication in comparison of standard knee injection post-operatively.
Time frame: Up to 1 month
Population: The vast majority of the patients had been discharged by 72 hours post-op, making this outcome low-powered and not useful. Because of this we used the 48 hour pain measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EXPAREL® Bupivacaine Liposome Suspension | Post-operative Complications | 0 complications |
| Standard Periarticular Joint Injection | Post-operative Complications | 0 complications |
Secondary
Recovery Room Opioid Use
Post anesthesia care unit (recovery room) opioid use in total mg morphine IV equivalent in comparison of standard knee injection post-operatively.
Time frame: Up to 48 hours
Population: The vast majority of the patients had been discharged by 72 hours post-op, making this outcome low-powered and not useful. Because of this we used the 48 hour pain measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EXPAREL® Bupivacaine Liposome Suspension | Recovery Room Opioid Use | 5 Total morphine equivalents |
| Standard Periarticular Joint Injection | Recovery Room Opioid Use | 5 Total morphine equivalents |