Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05635916 |
| Other study ID # |
155 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
September 22, 2022 |
| Est. completion date |
April 17, 2023 |
Study information
| Verified date |
July 2023 |
| Source |
Northern Light Mercy Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Total knee arthroplasty (TKA), also known as a knee replacement, is a procedure performed to
reduce severe pain and improve function of the joint. Managing postoperative pain can be
challenging following TKA, and inadequate relief can lead to impaired mobility and persistent
opioid use. Adductor canal nerve blocks (ACB), have shown significant benefit in improving
postoperative analgesia and patient satisfaction. However, the local anesthetic used
currently for these blocks only provides temporary relief that wears off within 24 hours.
Liposomal bupivacaine is an extended-release local anesthetic agent that can provide up to 72
hours of pain relief, however it is unclear if its use is also effective in ACBs for knee
surgery. The purpose of this study is to determine if liposomal bupivacaine is better than
conventional bupivacaine in improving pain control, opioid consumption, and length of stay in
patients scheduled for TKA.
Description:
BACKGROUND The femoral nerve block and the adductor canal nerve block are two regional
anesthesia techniques used to manage pain control following TKA Femoral nerve blocks were the
first peripheral nerve block employed for post-surgical analgesia, however they are now less
frequently used due to significant drawbacks that influence recovery. The femoral nerve
provides motor and sensory innervation to the quadriceps muscle. Blockade of the motor
branches of this nerve leads to quadriceps weakness and increased risk of falling after
surgery. Additionally, for similar reasons, ambulation after surgery can be significantly
delayed. In contrast, the adductor canal block does not affect the quadriceps muscle, as it
avoids the motor branches of the femoral nerve. The location of the block, located in the
mid-thigh, mainly affects the sensory neuronal branches of the saphenous nerve. It has been
found as a superior method for post-surgical analgesia since motor weakness is spared.
The adductor canal block is an interfascial plane block that can be performed as a single
injection, or as a continuous infusion via insertion of a catheter. Continuous peripheral
nerve blocks can provide prolonged post-operative analgesia, however, they are associated
with several complications including catheter infection, obstructions, and fluid leakage
Catheter placement takes a significant amount of time to perform and can consume valuable
clinical resources. Additionally, catheter displacement can be frequent with ACBs, since the
aponeurosis where the saphenous nerve lies is superficial, leading to easy dislodgement and
block failure. In comparison, a single injection of local anesthetic in the adductor canal
space is much simpler to place, is more cost effective, and has a lower infection risk.
However, risk of rebound pain is much higher in single injection nerve blocks due to their
shorter duration of action.
Liposomal bupivacaine (LB) is an extended-release local anesthetic that combines the benefits
of a single injection nerve block with the long-lasting effects of continuous catheter
infusions. LB received Food and Drug Administration approval in October 2011 for
post-surgical anesthesia via local infiltration and, in April 2018, for interscalene brachial
plexus blocks. LB has been reported to provide analgesia for up to 72 hours, making it the
longest lasting local anesthetic currently available.
There have been several studies evaluating the effectiveness of perineural LB in improving
peripheral nerve block analgesia compared to non-liposomal anesthetics for total knee
arthroplasty but the evidence is not definitive. A meta-analysis performed found that LB was
associated with higher pain relief compared to traditional bupivacaine and reduced opioid
related complications in TKA patients. Another study found decreased opioid consumption and
improved pain scores within the early post-operative period following TKA, but there was no
significant difference in length of hospital stay, patient satisfaction, or adverse
postoperative events. Another study found patients receiving LB for TKA had no improvement in
narcotic use, length of stay, patient reported pain, or functional ability compared to those
who received a single shot short acting ropivacaine nerve block. A recent meta-analysis
concluded that perineural infiltration of LB in various, distinct peripheral nerve block
locations was not superior to non-liposomal bupivacaine.
There is an institutional desire to improve postoperative pain outcomes and shorten length of
stay in patients undergoing TKA. It is possible that liposomal bupivacaine may help improve
these measures, however, current evidence is inconclusive. The purpose of this study is to
investigate the analgesic efficacy of liposomal bupivacaine comparative to conventional
bupivacaine in ACBs for individuals undergoing TKA.
SPECIFIC AIMS AND OVERALL SIGNIFICANCE Through this prospective trial, we aim to gather
institutional data investigating the effectiveness of liposomal bupivacaine compared to
conventional bupivacaine for the management of post-total knee arthroplasty pain.
Specific Aims Aim 1: To compare the efficacy of liposomal bupivacaine to conventional
bupivacaine for adductor canal blocks in adults scheduled for total knee arthroplasty.
Aim 2: To compare postoperative opioid consumption measured as morphine milligram equivalents
(MME) at 24 hours postoperatively.
Aim 3: To compare postoperative pain scores and opioid consumption at 48 and 72 hours after
surgery.
Aim 4: To compare total length of postoperative stay following surgical stop time.
Significance This study is significant because there is conflicting evidence regarding the
efficacy of liposomal bupivacaine. Currently, liposomal bupivacaine is used routinely at our
institution for surgical wound infiltration. Liposomal bupivacaine is also routinely used at
our institution for targeted peripheral nerve blocks for shoulder surgery.
Total knee arthroplasty is one of the most common surgeries performed to relieve joint pain
in those suffering from arthritis of the knee.1 TKA is a procedure met with moderate to
severe post-operative pain that affects early ambulation, range of motion, post-operative
rehabilitation, patient satisfaction, and patient outcomes.1 Identifying optimal strategies
to decrease acute pain is crucial for improving post-surgical outcomes in these patients.
Although, similar to liposomal bupivacaine, continuous perineural catheters (PNC) can
potentially provide greater than 24 hours pain relief while single shot nerve blocks with
conventional local anesthetics typically provide less than 24 hours of pain relief, there are
many factors which can impair PNC efficacy and their routine use for adductor canal blocks
has fallen out of favor in recent years. Catheter placement can be quite challenging which
can lead to block failure. Also, catheters can become dislodged, leak at the insertion site,
and commonly get disconnected from the local anesthetic infusion pump, leading to
interruption of analgesia. Since PNCs are an inserted foreign body, they carry a risk of
infection greater than single shot local anesthetic techniques. Identifying an easy, reliable
approach to provide multi-day pain relief will benefit patient care as well as current
procedural and postoperative care workflows.
If our study reveals that liposomal bupivacaine can provide superior analgesia to standard
single injection bupivacaine, this can have a profound impact on the future of post-TKA pain
management.
MATERIALS AND METHODS This is a prospective, randomized, clinical trial comparing adductor
canal blocks using liposomal bupivacaine to conventional bupivacaine for patients scheduled
for total knee arthroplasty. Patients enrolled in this study will include those that are 18
years or older undergoing primary total knee arthroplasty and ASA class I-III. Patients that
will be excluded are those that are unable to cooperate or consent to the study, have
allergies to local anesthetics, have an infection at the needle insertion site, BMI >40
kg/m2, history of coagulopathy, substance use disorder diagnosis, and patients using opioids
with greater than 90 MME/day.
STUDY PROTOCOL On the day of surgery, the anesthesiologist will elicit and answer any
questions or concerns regarding the study. Patients will be informed of the potential risks
and complications of nerve block placement that are inherent to their scheduled anesthetic
and independent of their participation in the study. These include bleeding, infection, and
potential nerve injury. Informed consent will be obtained from patients who were introduced
to the study prior to the day of surgery and decide to enroll in the study.
After informed consent is obtained, patients will be randomized into the two study groups in
a 1:1 ratio as follows:
Intervention arm: Adductor canal block with injection of 10cc 13.3% liposomal bupivacaine
combined with 10cc 0.25% bupivacaine within one hour following surgery Control arm: Adductor
canal block with injection of 20cc 0.5% bupivacaine within one hour following surgery
(current standard practice) The randomization scheme will be developed using NQuery Software
(Statistical Solutions, Boston, MA). The analyst will provide the research coordinator with
randomization assignments in sequentially-numbered opaque envelopes. As the study is
unblinded, both patients and providers will be aware of the randomization assignment. To help
mitigate bias, the team members collecting and entering data will be masked regarding the
patient's assignment. The REDCap database has the randomization assignments in an instrument
separate from the study data collection instruments, allowing for data entry without seeing
which group the subject is in.
The ultrasound guided nerve blocks will be performed by experienced study staff members of
the regional anesthesia team. Patients will be placed on standard ASA monitors and given
supplemental O2 via nasal cannula or simple mask. The injection site(s) will be prepped and
draped using standard infection control and sterile protocols. Light sedation will be given
as needed by the attending anesthesiologist, and skin infiltration of the puncture site with
2% lidocaine will be performed.
An ultrasound will be used to visualize the saphenous nerve and any relevant structures.
After the targeted nerve structures have been identified, the peripheral nerve block needle
will be advanced under direct ultrasound visualization. Following negative aspiration of
blood and air, the study drug will be deposited in the immediate vicinity of the saphenous
nerve using low pressure injections.
In the event of poorly controlled pain at any point during the study, we will provide the
patient with appropriate analgesic rescue agents to ensure that post-surgical pain is
adequately controlled. All pain medications will be documented for subsequent analysis.
Outcome data will be collected by a blinded member of the anesthesia research team as
outlined in the data collection table. Vital signs, NRS pain scores, and adverse symptoms
will be recorded in the subject's medical record as standard practice. This information will
be collected for study purposes.
If a participant decides to withdraw from the study prior to the 72 hour time point, data
collected prior to withdrawal will be included in the study unless the subject requests that
their data be removed from the study database.
