Comparison of continuous peripheral nerve block and continuous periarticular infiltration to prolong analgesia in total knee arthroplasty: an executive summary of evidence

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METHODS TO PROLONG POSTOP ANALGESIA IN TKAS
May 2024

COMPARISON OF CONTINUOUS PERIPHERAL NERVE BLOCK AND CONTINUOUS
PERIARTICULAR INFILTRATION TO PROLONG ANALGESIA IN TOTAL KNEE
ARTHROPLASTY: AN EXECUTIVE SUMMARY OF EVIDENCE

by

Joyce Pan
University of Southern California
Los Angeles, California

A Doctoral Capstone Presented to the
FACULTY OF THE USC KECK SCHOOL OF MEDICINE
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the Requirements for the Degree
DOCTOR OF NURSE ANESTHESIA PRACTICE
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METHODS TO PROLONG POSTOP ANALGESIA IN TKAS

Distribution of Work

The following manuscript was contributed to in equal parts by Jared Cheves, Amanda
DeChent, Joyce Pan.

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Dedication
For all the anesthesia providers dedicated to life-long learning who champion healthcare
innovation and push the boundaries to provide high quality patient care.

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Acknowledgements
This paper would not have been possible without the support from the faculty of the
Doctor of Nurse Anesthesia Program at the University of Southern California. Our fearless
capstone faculty chair, Dr. Charles Griffis, provided us with countless hours of counseling and
hearty conversations that challenged us to reach beyond what we thought was possible and
refined our research endeavors. We are honored to have the opportunity to work with a man who
has dedicated his life to the advancement of anesthesia and mentorship of future anesthesia
professionals.

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Table of Contents
Dedication ...................................................................................................................................... iii
Acknowledgements ........................................................................................................................ iv
Table of Contents ............................................................................................................................ v
Abstract .......................................................................................................................................... vi
Chapter 1 ......................................................................................................................................... 7
Introduction ................................................................................................................................. 7
Research Question and Specific Aims ...................................................................................... 14
Background and Significance ................................................................................................... 14
Factors Predicting Joint Surgery ........................................................................................... 14
Postoperative Pain and Joint Arthroplasty ............................................................................ 15
Risks of Opioid Analgesia .................................................................................................... 16
Shift to Ambulatory Surgery ................................................................................................. 17
Advantages, and Limitations of PNB and PAI Techniques .................................................. 19
Clinical Problem ................................................................................................................... 21
Chapter 2 ....................................................................................................................................... 23
Methods..................................................................................................................................... 23
Chapter 3 ....................................................................................................................................... 25
Literature Review...................................................................................................................... 25
Continuous Peripheral Nerve Block (CPNB) ....................................................................... 25
Continuous Peri-Articular Infiltration (CPAI) ...................................................................... 28
Investigations Comparing CPNB and CPAI for TKA Analgesia ......................................... 35
Chapter 4 ....................................................................................................................................... 40
Results ....................................................................................................................................... 40
Summary of CPNB when Compared to Standard Postoperative Opioid Use ...................... 41
Summary of CPAI when Compared to Standard Postoperative Opioid Use ........................ 42
Summary of CPNB Compared to CPAI ............................................................................... 44
Chapter 5 ....................................................................................................................................... 46
Discussion ................................................................................................................................. 46
References ..................................................................................................................................... 54
Figures........................................................................................................................................... 67
Tables ............................................................................................................................................ 69

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Abstract
Total knee replacements (TKAs) are one of the most common but painful surgical procedures
performed in the United States. Currently, the gold standard for postoperative pain management
is the utilization of opioids. However, in the wake of the opioid epidemic, the healthcare system
is attempting to reduce opioid consumption by trialing innovative opioid sparing techniques such
as continuous peripheral nerve blocks (CPNB) and continuous periarticular infiltration
(CPAI). Analgesia, particularly during the first 72 hr postoperatively, is vital due to its
association with delayed recovery, impaired rehabilitation, immunosuppression, the development
of chronic pain and rebound pain, and decreased patient satisfaction. While both techniques are
being used today, there is limited evidence comparing them to the current standard of care or to
each other. An extensive literature review was performed to explore the safety profiles and
effectiveness of CPNB and CPAI in reducing pain scores and opioid consumption. The literature
revealed the usage of CPNB contributed to lower pain scores and decreased opioid use when
compared to opioid-only control groups. Additionally, CPAI did not improve pain scores or
decrease opioid consumption when combined with a multimodal analgesic (MMA) regimen.
When comparing CPNB and CPAI to each other, neither unanimously lowered pain scores, but
the literature indicates that CPNB decreased opioid consumption more than CPAI. More research
is needed to further cement the efficacy of CPNB and CPAI as standard components of MMA in
TKA procedures. Future research can also focus on novel catheter-free applications to reduce the
complications of continuous catheter analgesics.
Keywords: Total knee arthroplasty, continuous peripheral nerve blocks, continuous periarticular
infiltration, opioid, multimodal analgesia
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Chapter 1
Introduction
Surgical procedures involving joints- arthroplasties- are among the most painful surgeries
and lead to intense postsurgical discomfort (Krishna Prasad, 2020). Between the years 2012 and
2019, 53% of all orthopedic surgeries were total knee arthroplasties (TKA) (American Academy
of Orthopedic Surgeons, 2020), with an estimated 3.5 million TKAs projected to be performed
annually by 2030 (Weinstein et al., 2013).
Total knee arthroplasties, like most surgical interventions, have relied on opioids to
adequately treat pain throughout the perioperative period (Hannon et al., 2020). The utilization of
opioids throughout the perioperative period has been proven effective and reliable in providing
pain control following general anesthesia (Hannon et al., 2020). However, multiple serious,
short-term, and long-term complications are associated with opioid analgesia (Alexander et al.,
2019; Trasolini et al., 2018). These associated risks, along with the burgeoning opioid epidemic,
have shifted the United States healthcare system towards an “opioid-sparing” approach in all
care settings, including the perioperative period. (Shanthanna et al., 2021). Utilizing less invasive
procedures and opioid-sparing approaches has improved patient recovery and minimized
perioperative complications (Migliorini et al., 2021; Moutzouros et al., 2020). These practice
improvements have facilitated the nationwide movement towards ambulatory surgery settings as
the primary location for low to intermediate-risk procedures (Hoffman et al., 2018). For this
reason, it is imperative that opioid-sparing analgesic alternatives are established and available for
pain management providers throughout the perioperative period.
In an effort to decrease the use of opioids, a new approach to analgesia has emerged that
combines various categories of non-narcotic analgesic drugs. These combinations include
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medications administered through systemic routes, injections for sensory nerve blocks, local
infiltrations of joints and surgical sites, and/or needle-free applications to the surgical site
(Goode et al., 2019; Gabriel et al., 2019). Providers adopted this blending of therapeutics as
components of multimodal analgesia or multimodal pain management (MMA) (Chung &
Spangehl, 2018; Moutzouros et al., 2020). The American Medical Association (2019) defines
multimodal pain management as “the use of two or more non-opioid medications that act by
different mechanisms to provide analgesia” (p. 2). Multimodal pain management protocols
strategically manipulate the medication timing, routes, and classification, to synergistically
enhance analgesia (Moutzouros et al., 2020).
To further emphasize the importance of MMA, in 2019, a multi-society organization
reached a consensus through the US Health and Human Services Pain Management Best
Practices Inter-Agency Task Force regarding guiding principles for acute perioperative pain
management (Mariano et al., 2022). Organizations such as the American Society of
Anesthesiologists (ASA), the American College of Surgeons (ACS), the American Society of
Regional Anesthesia and Pain Medicine (ASRA), and several others, determined that the
evolution of pain management will require “individualized, multimodal., and multidisciplinary
approaches to pain management that decrease the over-reliance on opioids” (Mariano et al.,
2022, p.1).
In addition to discussing the various modalities available for pain management, this
paper’s primary topic of clinical relevance is the “duration of analgesia”. The pain level present
in the acute postoperative period has significant implications for patient outcomes. Inadequately
controlled pain in the immediate postoperative period has been associated with delayed recovery,
impaired rehabilitation, immunosuppression, the development of chronic pain, and decreased
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patient satisfaction (Richebé et al., 2018). The postoperative pain arc peaks within the first 72 hr
and to avoid the negative consequences of inadequate pain management, practitioners should
investigate methods that provide analgesia up to and beyond the pain peak point of 72 hr
(Svensson et al., 2000). As previously stated, TKAs are recognized as one of the most painful
orthopedic procedures, so pain management is vital, and the exploration of available techniques
that provide the longest coverage with the least number of complications is necessary.
Regional anesthesia, such as peripheral nerve blocks (PNBs) of the femoral nerve, sciatic
nerve, and/or obturator nerve, have become major components of MMA protocols for TKA
procedures, displaying effectiveness in providing analgesia through sensory blockade (Qin et al.,
2021). Peripheral nerve blocks are a type of regional anesthesia in which local anesthetics (LA)
are injected near a bundle of nerves to produce the loss of sensation or mobility. There is
evidence that PNBs can accomplish sensory blockade and possess several benefits that opioid-
inclusive general and epidural anesthesia fall short of, such as reduced length of hospital stays,
earlier participation in physical rehabilitation, decreased opioid consumption, and a reduced
incidence of postoperative nausea and vomiting, while avoiding common side effects of opioids
such as postoperative hypotension and urinary retention (Cosowicz et al., 2016; Fredrickson &
Kilfoyle, 2009; Gaukhman et al., 2020). Despite an expanding pool of evidence to support the
efficacy of PNBs in providing intraprocedural sensory loss with minimal complications,
postoperative opioids remain the main type of analgesia delivered for TKAs for postoperative
pain relief, begging the question – do PNBs provide adequate and timely postoperative
analgesia? (Cosowicz et al., 2016; Johnson et al., 2016; Turnbull et al., 2017).
It is important to consider the advantages and disadvantages of the PNB technique, as
these impact the outpatient surgical experience. While PNBs performed as a one-time injection
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of LAs (“single-shot technique”) may provide excellent intra- and postoperative analgesia, this
approach is limited by the duration of analgesia and the high risk for rebound pain in the
postoperative period at discharge (Joshi, 2016).
Single-shot PNB procedures consist of one injection of LA near the nerve to block
sensory pain signals. Local Anesthetics are often chosen based on their duration of action (DOA)
and for this reason, the most commonly used include intermediate amide-linked formulations
such as lidocaine, and longer-acting amide formulations such as bupivacaine and ropivacaine
(Moucha, 2016). Their mechanism of action is to decrease the transmission of pain signals
through reversible blockage of voltage-gated sodium and potassium channels in nociceptive pain
fibers (Ross et al., 2017). However, the duration of action producing clinically relevant analgesia
rarely lasts longer than 12-24 hr following a single injection (Moucha, 2016). Thus, due to
postoperative pain peaking within the first 72 hr, there is a risk of significant postoperative
rebound pain with a single-shot PNB administration once the sensory block has worn off
(Svensson et al., 2000). Additionally, a systematic review conducted in the ambulatory surgery
setting provided evidence that one of the major factors that resulted in failed discharge was
inadequate analgesia at the surgical site, along with other identified factors including
hypotension and nausea (Hoffmann et al., 2017). This further emphasizes the importance of
developing efficacious, reliable, and safe postoperative analgesia approaches that are effective
during the critical 72 hr postoperative period for this patient population.
Another technique to provide prolonged analgesia postoperatively that has been
developed as an alternative to opioids is local infiltration analgesia (LIA). It has recently grown
in popularity among researchers and clinicians and is also referred to throughout the literature as
periarticular infiltration (the term “infiltration”, combined with “local and analgesia”, is used
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interchangeably with “injection/installation” to describe the same technique, which will be
abbreviated as “PAI'' in this paper). Periarticular infiltrations, as an analgesic adjunct, consists of
injecting a solution containing multiple analgesics of various classes into or near the surgical
site, which may include long-acting local anesthetics, anti-inflammatory agents, nonsteroidal
anti-inflammatory drugs, opioids, ketamine, and steroids. (Gabriel et al., 2019; Raeder & Spreng,
2020). Periarticular infiltrations improves pain scores and lowers opioid consumption
(Seangleulur et al., 2016). Like single-shot PNBs, single-injection PAI can be limited in efficacy
by its duration of analgesia, which has been found to last approximately 8-12 hr postoperatively.
However, in some instances, typical bupivacaine and ropivacaine formulations may last up to 48
hr postoperatively (Sun et al., 2016).
Long-acting formulations of LAs are an important point of discussion when considering
techniques used to prolong analgesia postoperatively. As stated above, bupivacaine and
ropivacaine are strategically chosen because they provide the longest DOA available when
compared to other class equivalents. However, blocks using these agents have often fallen short
in reliably providing analgesia past the first postoperative day (Gabriel et al., 2019). There have
been several formulary advancements that have modified bupivacaine in an attempt to prolong
its duration of efficacy by creating extended-release formulations. With particular relevance to
PNBs, the FDA granted approval of liposomal bupivacaine (Exparel ®) in 2011.
At the time of Exparel’s introduction, early evidence supported that the shortcomings of
PNBs (i.e., limited DOA) would be alleviated with its novel extended-release formulation.
However, more recent evidence consistently demonstrates that Exparel is not superior to
standard formulations in decreasing pain and decreasing opioid consumption, as described in the
executive summary of randomized control trials (RCTs) by Ilfeld et al. (2018). Of the 13 RCTs
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that investigated the ability of Exparel to extend analgesia during the critical 72 hr postoperative
period and decrease opioid consumption compared to non-liposomal long-acting local
anesthetics (bupivacaine and ropivacaine), 11 of the studies did not demonstrate superior
efficacy with the use of Exparel (Ilfeld et al., 2018). In fact, as of 2020, the International
Congress for Joint Reconstruction (ICJR) issued a statement concurring that current systematic
reviews and meta-analyses do not support the clinical benefits of liposomal bupivacaine as a
single-shot technique in either PNBs or PAIs (Gaukhman et al., 2020). Exparel’s formulation is
approximately 100 times more expensive than the standard alternatives. The lack of exceptional
efficacy and high costs has limited the success of Exparel as an option for analgesia of sufficient
DOA for TKA procedures.
As detailed above, single shot PNB, single shot PAI, and prolonged duration LA’s (e. g.
Exparel) in these approaches, do not reliably provide adequate pain control throughout the
critical 72 hr postoperative pain period without relying on opioids. A modification to these
interventions, to extend the duration of action, is to provide continuous peripheral analgesia via
an indwelling catheter, which is placed to deliver medications either to the nerve plexus
innervating the surgical site (peripheral nerve block), or directly to the surgical site or joint itself
(peripheral articular infiltration) (Rodriguez-Patarroyo et al., 2021).
Both PNBs and PAIs can be used as continuous infusions (CPNBs and CPAIs); the
catheters are placed in the target location under ultrasound guidance and then connected to
infusion pumps. Infusions usually consist of local anesthetics, such as bupivacaine and
ropivacaine. The duration of action of the medication itself remains similar to the single-shot
counterparts, but the main difference is that the catheter allows for continuous administration,
which extends the duration of analgesia. When considering the absence of effective extended-
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release LAs the indwelling catheter techniques may be one of the only complete non-opioid
methods of providing sufficient analgesia far enough into the critical 72 hr postoperative period
(Soffin & Memtsoudis, 2018). Both continuous infusion PNBs and PAIs are being used in
practice today, but there is limited evidence comparing the two applications to the current
standard of postoperative opioids and each other.
The evolution of analgesia techniques for postoperative TKAs is quickly expanding
outside the realm of opioids and requires a thorough review of the literature to evaluate the
benefits and disadvantages of two such approaches: continuous peripheral nerve blocks (CPNBs)
and continuous periarticular infiltration (CPAIs). This capstone project will investigate the
current literature on the effectiveness of utilizing CPNBs and CPAIs as techniques to prolong the
duration of analgesia in postoperative TKA patients. Effectiveness will be ascertained based on
the ability of these techniques to decrease standardized patient-reported pain scores and to reduce
opioid consumption based on patient record review. Please see Table 1 – Glossary of
Operational Terms – for all relevant terms, abbreviations, and definitions as they pertain to this
introductory paragraph. (page 69.)

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Research Question and Specific Aims
The Population/Intervention/Outcome (PIO) question guiding this evidence-based
investigation is: When comparing continuous peripheral nerve blocks (CPNBs) and continuous
periarticular local anesthetic infiltrations (CPAIs), which approach provides the most efficacious
and safe postoperative analgesia while minimizing the use of opioids for total knee arthroplasty
patients?
The specific aims include:
1. Perform a critical and systematic literature review of the efficacy and safety of CPNB and
CPAI in prolonging duration of effective analgesia into the postoperative period after
total knee arthroplasty.
2. Synthesize and provide an executive summary of the literature regarding the efficacies
and limitations of continuous peripheral nerve blocks and continuous periarticular local
anesthetic infiltration in providing prolonged, effective, and safe analgesia in the
postoperative period. The duration of action and effectiveness will be measured by
standardized pain scores and the amount of opioid consumed at reported postoperative
time intervals.
Background and Significance
Factors Predicting Joint Surgery
Joint disease is a common morbidity among the elderly population - osteoarthritis, in
particular, is the most common type, with an incidence rate of 10% in females and 13% in males
over the age of 60 years (Zhang & Jordan, 2011). The United States population is perpetually
becoming a disproportionately older demographic. The 2017 United States Census Bureau’s
National Population Projections Report estimates that by 2030 approximately 77 million people
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will be over the age of 65 years, surpassing the number of people under the age of 18 for the first
time in American history (Vespa et al., 2018). With old age and obesity as the most significant
risk factors for developing symptomatic osteoarthritis (Zhang & Jordan, 2011), often of the knee
and hip, it is not a surprise that Weinstein and Rome (2013) estimate around 3.5 million TKAs to
be performed annually by 2030.
Postoperative Pain and Joint Arthroplasty
The documented prevalence of severe acute pain after TKAs varies throughout the
currently available literature. However, a prospective cohort study with 242 participants,
reported an incidence of 70% of patients endorsed moderate to severe acute pain on
postoperative day (POD) one after total knee replacement (Alameri et al., 2020). With concerns
to the prevalence of moderate to severe pain extending into the critical 72 hr period
postoperatively, a systematic literature review, conducted by Grasu et al. (2014), revealed that
45% of TKA patients reported a Numeric Pain Score rating of >4 on postoperative day (POD) 3
and up to 57% of patients reported sleep disturbances related to pain on POD 3. Through
advancements in minimally invasive techniques and utilization of multimodal analgesic
protocols, the intensity and duration of pain that a patient experiences in the postoperative period
have improved; however, the problem of inadequate analgesia in the critical 72 hr postoperative
period persists (see Figure 1) (Grasu et al., 2014; Lo et al., 2021). Providing prolonged analgesia
is paramount for positive patient outcomes in the postoperative period because severe or
uncontrolled pain during this period has been associated with decreased patient satisfaction,
prolonged hospital stays, increased incidence of pulmonary and cardiac complications, delayed
physical therapy and rehabilitation, development of chronic pain, and increased mortality (Desai
et al., 2021; Grasu et al., 2014; Terkawi, 2017). To further highlight the importance of reaching
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sufficient and prolonged analgesia in the postoperative period, Wells et al. (2008) found that
patients who do not achieve adequate pain control in the first 48 hr postoperatively may be
limited to a 50% chance of achieving long-term satisfactory pain relief.
Risks of Opioid Analgesia
Historically, opioids have long been an essential component of most pain management
plans throughout the perioperative period because their analgesic properties are extremely
effective and predictable (Hannon et al., 2020). The trend toward increased and more liberal use
of opioids in pain treatment began in the 1990’s and early 2000’s in response to the increasing
recognition of the importance of effective pain treatment, which was widely found to be
inadequate prior to this time period (Jones & Viswanath, 2018). One of the movements guiding
improved pain assessment and treatment was the World Health Organization’s initiative against
the under-treatment of pain (Campbell, 2016). This initiative came about in response to
numerous reports of inadequate diagnosis and treatment of pain. In response, care providers
shifted their focus by recognizing pain as the “5
th
vital sign”. The usage of opioids, which have
historically been recognized as the most effective analgesic agent, surged after this emerging
practice change. As a result, opioid-related adverse side effects in certain patient populations
increased.
Despite obvious benefits, opioids are accompanied by a comprehensive list of short-term
and long-term complications (Alexander et al., 2019). Common adverse effects that are
associated with the perioperative period include, but are not limited to: respiratory depression,
pruritus, ileus, nausea, vomiting, constipation, urinary retention, hypotension, bradycardia,
delayed emergence and potentially failed extubation at the conclusion of surgery. Abuse and
misuse of opioids leading to dependence and addiction is the most notable long-term
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complication of opioid use and a significant contributor to the current opioid misuse and
overdose epidemic in the United States (Trasolini et al., 2018). The number of opioid overdose
related deaths has been growing exponentially over the last several decades; the most recent
reports from the Centers for Disease Control and Prevention (CDC) indicate that nearly 50,000
deaths related to opioid overdose occurred in 2019 (Center for Disease Control and Prevention
[CDC], 2021).
A notable percentage of surgical patients have their first exposure to opioids after
obtaining a legal prescription from a medical provider and are at risk for developing chronic
opioid dependence persisting beyond the analgesic needs of the surgery (Trasolini et al., 2018).
A retrospective analysis of 641,941 opioid-naive surgical patients showed that surgical
procedures are associated with an increased risk of chronic opioid use, and 1.41% of TKA
patients will develop chronic opioid use (when compared to 0.136% in the non-surgical patient
population (Sun et al., 2016). As a result of this evolving public health crisis, healthcare
professionals have been more cautiously prescribing opioids to lessen the public’s exposure to
highly addictive opioid drugs (Trasolini et al., 2018), providing additional impetus for the current
investigation of alternative non-opioid analgesic methods.
Shift to Ambulatory Surgery
Considering all the negative impacts of opioids is particularly important when
perioperative patients receive care in the ambulatory setting (Hoffman et al., 2017). Numerous
terms describe surgical procedures that do not require an overnight stay, such as same-day
surgery, ambulatory surgery, outpatient surgery, and office-based surgery. To remain consistent,
this investigation will use the term “ambulatory surgery” to describe surgery when the patient is
expected to return to a home setting for recovery during the 72 hr following the procedure.
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The United States healthcare system strives to decrease costs and improve profit margins
while maintaining safety and improving outcomes. To achieve these goals, there has been a
major shift toward performing TKAs in the outpatient setting within the last several decades.
Investigators conducted a systematic review (Hoffman et al., 2017), which analyzed over 1000
patient arthroplasty encounters throughout ten randomized control trials, with nearly all patients
utilizing neuraxial (NA) or peripheral nerve block (PNB) and a minority using general
anesthesia. Substantial evidence supports the safety and cost-effectiveness of TKAs performed
with the goal of same-day discharge. Of the cumulative patient population, 94.7% were
discharged on the same day, with only one patient having a major complication (ischemia
requiring coronary artery angioplasty) and eight patients having a minor complication (stress
fracture, UTI, anemia, foot drop, hematoma). Additionally, Lovald et al. (2014) conducted a cost
analysis revealing that inpatient TKA (3-4 days) costs $8,527 more than an outpatient equivalent
TKA procedure (<1 day) conducted in the ambulatory setting.
Nationally recognized leaders of regional anesthesia at The New York School of
Regional Anesthesia (NYSORA), among others, believe that this practice shift to fast-tracked
outpatient TKA will require minimizing the use of general anesthesia and increasing the use of
NA and PNB techniques to maintain patient safety, outcomes, and satisfaction (Hoffmann et al.,
2017; Spofford et al. 2022). When considering the safety profile and cost effectiveness of
outpatient TKAs, Bovonratwet et al. (2017) found that only 0.57% of patients eligible for
outpatient TKA (out of 112,922 outpatients on the American College of Surgeons – National
Surgical Quality Improvement Program [ACS-NSQIP] database) were treated on an outpatient
basis. This opportunity for cost savings while maintaining patient safety/satisfaction is an
incentive to increase the availability of non-opioid, effective analgesic techniques, facilitating
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adoption of outpatient TKA, and minimizing opioid usage. A database analysis of over one
million knee and hip arthroscopic procedures revealed that from 2006 to 2013, PNBs used for
TKA increased from 11.7% to 32.6%, with predictions of increased utilization annually
(Cosowicz et al., 2016), indicating this practice shift is underway.
Advantages, and Limitations of PNB and PAI Techniques
Reported complications and limitations of PNBs include decreased quadricep mobility
and strength from motor blockade, leading to increased risk of falls and peripheral nerve
dysesthesia (Moucha et al., 2016). Regarding risks with associated motor nerve blockade,
Charous et al. (2011) found a reduction of quadricep strength of more than 80% after a femoral
nerve block (FNB), which is not ideal for patients recovering from a surgery that requires early
mobilization and rehabilitation for optimal recovery. The incidence of peripheral nerve
dysesthesia, described as “tingling”, “numbness”, and “pins and needles”, is as high as 8.2%
according to Fredrickson and Kilfoyle (2009), who studied neurological complications of 1000
ultrasound guided PNBs for orthopedic surgeries.
Continuous peripheral nerve blocks, in which a catheter is inserted at the site and delivers
a continuous infusion of local analgesics, can potentially resolve suboptimal duration of
analgesia of “single- shot” PNBs. Salinas et al. (2006) reported that patients receiving a CPNB
reported lower mean visual analog scale (VAS) pain scores as compared to those who received
single-shot PNBs. However, CPNBs come with their own set of limitations, including the risk of
infection, catheter dislodgement, catheter obstruction, fluid leakage, technical skill required to
perform the procedure, time requirements, and numerous personnel needed for placement (often
a separate team), monitoring of the infusion, and various other institutional resources (Joshi et
al., 2016). Additionally, the logistical maintenance of keeping a multiday catheter in place during
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aggressive physical rehabilitation in outpatient ambulatory surgical populations is a challenge
(Gabriel et al., 2019). Typically, nurses manage CPNBs connected to infusion pumps. However,
several portable infusion pumps (such as the On-Q © Pain Relief System) are feasible options
for patient-managed indwelling catheters in the home setting. Hanson et al. corroborated the
efficacy and safety of these systems, showing that portable infusion devices in 69 eligible
patients were effective in maintaining adequate analgesia (pain scores <2 at rest, <4 with
activity) with no incidence of rebound pain, unintentional catheter dislodgement, falls, or
dysesthesias (2016). Nevertheless, this additional equipment imposes potential costs and
challenges to elderly patients in the home setting following major joint replacement surgery.
As a result of the limitations of single-shot and continuous PNB, research initiatives to
find alternative analgesia methods and adjunct techniques to regional anesthesia have been
ongoing. PAI emerged as a potential option for treating perioperative pain associated with TKAs
(Seangleulur et al., 2016). Kerr and Kohan introduced PAI to orthopedic surgeries as its modern
iteration in 2008. Their team used the term local infiltration analgesia (LIA), previously
described in this paper as equivalent to PAI. These investigators described the technique as
“systematic infiltration of a mixture of ropivacaine, ketorolac, and adrenaline into the tissues
around the surgical field to achieve satisfactory pain control with little physiological
disturbance” (Kerr & Kohan, 2008, p. 174). The technique of PAI has become a promising
adjunct for controlling acute pain because of its efficacy in pain relief, technically simple
application, and rare occurrence of complications such as associated infection and systemic
toxicity (Seangleulur et al., 2016).
The addition of a catheter infusion with PAI to produce CPAI has potentially added more
utility to this postoperative TKA pain management technique (Sun et al., 2015). However, the
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practice has not been universally adopted and little consensus has been reached regarding its
utility as a continuous infusion in comparison to CPNB.
Clinical Problem
The clinical problem addressed by this investigation is the lack of efficacious,
complication-free, non-opioid pain therapies that prolong analgesia beyond what current options
provide into the postoperative period and facilitate rapid discharge of post-TKA patients home in
the outpatient setting.
As previously discussed, PNBs and PAI are used as approaches to wound infiltration to
assure postoperative analgesia (Rodriguez-Patarroyo et al., 2021). The advantage of these non-
opioid approaches is achieving efficacious analgesia while avoiding opioid-associated
complications. Due to the minimally invasive nature of these techniques, ability to specifically
target a location or area, and comparably lower incidence of side effects, PNBs have become a
staple in the multimodal analgesia pathway, especially for surgical procedures of the extremities
(Gabriel et al., 2019; Gaukhman et al., 2020). According to Macfarlane et al. (2008) and Joshi et
al. (2016), research shows that PNBs decrease postoperative pain, reduce the use of opioids,
hasten postoperative rehabilitation, and reduce length of hospitalization. Single-shot femoral
PNBs showed a significant reduction in pain at rest and with movement at the 24 hr and 48 hr
postoperatively, along with a reduced postoperative opioid consumption at 48 hr (Joshi et al.,
2016).
However, evidence to support this duration of analgesia is limited when using the single-
shot PNB technique (Chan et al., 2014). These authors conducted a meta-analysis investigating
the use of various peripheral nerve block techniques and provided support that continuous
infusion femoral PNBs reduce pain at rest and with movement up to 48 to 72 hr postoperatively.
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The extended duration of analgesia produced by CPNB is invaluable to the overall goal of this
investigation. Due to the reduction in narcotic use, the adverse side effects of opioids, such as
urinary retention, constipation, nausea, and vomiting are significantly reduced (Moucha, 2016).
Overall, reported patient satisfaction with analgesia from femoral PNBs (both single shot and
continuous) is higher than that of patients who received opioids from parenterally administered
patient-controlled analgesia (PCA) (Chan et al., 2014).
Current postoperative pain management techniques for TKA can be improved. Opioids,
while effective for controlling pain, have many side effects, including respiratory depression,
nausea and vomiting, constipation, and potential dependence. Peripheral nerve block and PAI
utilize local anesthetics attempting to avoid these side effects of opioids, but their duration of
actions are not long enough to cover the 72 hr critical postoperative pain arc (see Figure 1).
Utilizing the indwelling catheters in CPNB and CPAI improves the duration of analgesia by
providing continuous local anesthetics to the site; however, these techniques have their own set
of limitations, such as a higher infection risk, risk of catheter mobilization, risk of falls due to
motor weakness, and challenges for patient management in the home setting. With the given
advantages and disadvantages of current practice, it is essential to compare the techniques to
determine the most effective pain management strategy for patients.
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Chapter 2
Methods
The authors addressed specific aim one through an extensive review of the existing
literature that investigates the use of CPNBs and CPAIs, to achieve prolonged analgesia for
patients undergoing total knee arthroplasty. The authors examined sources gathered from the
following databases: PubMed, Embase, Scopus, and Web of Science. The search terms used to
generate the articles for our primary literature review sources included: “Total Knee Arthroplasty
[Mesh]”, “Continuous”, “Catheter”, “Indwelling”, “Peripheral Nerve Block”, “Periarticular
Infiltration”, “Intra-articular Injection”, “Local Infiltration”, “Wound Infusion”, and
“Analgesia”. Inclusion criteria included articles published in English, after 2011, which reported
on the efficacy and limitations of two indwelling catheter-based methods of postoperative
analgesia for TKA in adults: CPBN and CPAI. The exclusion criteria included non-human
subjects, non-English language, non-adult participants <18 years old, and literature published
before 2011. The literature review included several seminal or classic articles critical to the
specific aims of the paper that fell outside of the defined time interval. Articles with control
groups that had exposure to epidural analgesia for comparison were excluded to improve the
association of CPAI/CPNB with reported outcomes. For improved homogeneity, these authors
included in the literature review only articles that had an intervention group (CPNB or CPAI)
compared to traditional opioid management techniques (patient-controlled analgesia [PCA] or
nurse-controlled “as needed” [PRN] opioid analgesia) measuring the effects on analgesic
duration and safety for analysis. To fully appreciate the value of each technique the articles that
explicitly compared CPNB to CPAI were incorporated. The “snowballing” technique was used;
all applicable article citations were screened, and any additional article abstracts relevant to the
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study-specific aims and meeting the inclusion and exclusion criteria were included for review.
See Figure 2 for a summary of the primary search methods for specific aim one displayed as a
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram.
The literature review results of specific aim one focused on two techniques of achieving
adequate, prolonged, complication-free postoperative analgesia for patients following TKA,
informed specific aim two. Namely, comparing continuous peripheral nerve blocks and
continuous peri-articular joint infiltration of local anesthesia. A literature analysis, looking at the
quality of evidence revealing comparative efficacy, benefits, drawbacks, and complications
associated with the two identified techniques, seen below in the results section. From this
analysis, the investigators synthesized an executive summary of the comparative effectiveness of
these approaches to postoperative analgesia for patients undergoing TKA as it currently exists.
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Chapter 3
Literature Review
Continuous Peripheral Nerve Block (CPNB)
Hanson et al. (2014) conducted a single-center, double-blinded trial evaluating
effectiveness of adductor canal blocks for postoperative analgesia (see Table 2 for a comparison
of the studies cited in this section). For the purpose of this investigation, adductor canal blocks
are considered a type of PNB. Amundson and Johnson (2022) describe adductor canal block as a
block performed in the thigh that provides primarily sensory anesthesia with less motor blockade
to the saphenous nerve, parts of the obturator nerve, and branches of the femoral nerve. It
enables safer, quicker ambulation and physical therapy due to its motor-sparing effects. In this
study, 76 patients were randomized into an intervention (block) and control group (sham catheter
in sartorius muscle, no medications or block). All patients received an ultrasound-guided FNB
with 20 mL 0.5% ropivacaine with epinephrine, spinal anesthetic with bupivacaine 12.5 mg, and
intra-procedural propofol sedation. The intervention group received an ultrasound-guided 19-
gauge epidural-type catheter advanced into the adductor canal and continuous infusion of
ropivacaine 0.2% at 8 mL/hr. Morphine consumption was measured by converting opioid
consumption into IV morphine milligram equivalents, documented here as mg of morphine
administered. Between 24-48 hr, the postoperative intervention block group consumed an
average of 30.5 mg of morphine compared to the control group, which consumed an average of
41.6 mg (p < .013); the intervention block group demonstrated improved ambulation on
postoperative day two (p < .034); and the intervention block group reported significantly reduced
median resting numeric rating scale (NRS) pain scores compared to the control group at
postoperative hr 18 (2 vs. 4, p =.009), hr 24 (3 vs. 5, p =.003), and hr 30 (3 vs. 4, p =.039). No
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adverse events were reported. One limitation this study faced was that a subset of subjects
received local infiltration, which could have affected the reduced morphine consumption.
However, the patients were equally distributed between the two groups, around 34% in each
group, and a post hoc analysis of morphine consumption revealed no statistically significant
difference in opioid consumption.
Leung et al. (2018) conducted a similar study that aimed to evaluate opioid consumption
after total knee arthroplasty with continuous adductor canal block versus sham catheter. Their
study was a 76-subject double-blinded, randomized, placebo-controlled trial. All patients
received an epidural or combined spinal-epidural depending on anesthesia evaluation according
to standard protocol. All patients had their epidurals removed on postoperative day one. After the
postoperative resolution of the epidural medication effects, investigators randomized patients
into either the intervention group that received the adductor canal block or the control group that
received the sham catheter. Pain specialists placed the adductor canal block in the intervention
group per standard protocol. To minimize invasiveness in the control group and to mimic the
procedures of the block placement, pain specialists utilized an ultrasound on the same area,
applied pressure with a wooden stick, and attached a catheter covered with an opaque dressing.
Both groups’ catheters were attached to identical pumps covered in opaque dressings to maintain
blinding control in the study. All patients in the study received the postoperative hospital pain
protocol that included: IV morphine 1-2 mg as needed, oxycodone extended-release 10 mg
tablets twice daily, tramadol 50 mg every 6 hr, and 1-2 tablets of hydrocodone/acetaminophen 5
mg-325 mg every 4-6 hr as needed. The study found that there was no significant difference in
morphine consumption between the two groups at the 12 hr mark, but at 20 hr postoperatively,
the sham catheter group required significantly more morphine than the adductor canal group
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(96.5 ± 47 mg vs. 73.9 ± 38 mg, p = 0.03). There was a significant decrease in pain scores (VAS,
0 mm = no pain; 100 mm = severe pain) in the catheter group 20 hr after placement (36.4 ± 18
mm vs. 28.6 ± 14 mm, p = 0.04) and functional status measured by the Likert-type 5 Point
Western Ontario and McMaster Universities (WOMAC) questionnaire, a valid and reliable
measure of pain, stiffness, and physical function of patients with osteoarthritis (Deveza, 2021),
was higher in the catheter group 3-weeks postoperatively compared to the control group (37.8 ±
13 vs. 29.1 ± 15, p = 0.04). Limitations of this study included the number of patients who
withdrew from the study due to failed epidural placement and fear of pain if they received the
sham catheter.
Nader et al. (2012) conducted a randomized controlled, parallel-group trial that focused
on long-term recovery after total knee replacement following the use of continuous FNB vs. oral
opioid analgesic in the postoperative period. Sixty-two patients were randomized into two
groups, one that would receive FNBs placed at the time of surgery, and activated
postoperatively, and another that would receive only oral opioid analgesics. Both groups
received patient-controlled epidural analgesia immediately after surgery in the PACU that
provided 3 mL/hr of bupivacaine 1 mg/mL and hydromorphone 10 µg/mL with patient demands
of 3 mL of the same solution and lockout times of 15 minutes. The epidural analgesia was
discontinued postoperative day 1, and the two groups were initiated. The FNB group received a
10 mL bolus of 0.25% bupivacaine initially and then a continuous infusion of 5 mL/hr of
ropivacaine 0.1%. They were also given opioids as needed if pain coverage was not sufficient,
which included hydrocodone 10 mg and acetaminophen 625 mg or if pain scores, using a Verbal
Rating Score for Pain (VRSP) ranging 0-10, could not be controlled under a score of 4. The
opioids were eventually switched to oxycodone 10 mg extended release every 12 hr and
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hydromorphone 2 mg every 4 hr. The opioid group only received the opioids listed previously as
needed on postoperative day 2. The study demonstrated that the continuous FNB group had
reported lower pain scores than the opioid-only group (Verbal Rating Score for Pain 0-10; 0 vs. 3
at 11 am, p = 0.024; 2 vs. 4 at 7 pm, p = 0.002; 1 vs. 4 at 3 am, p = 0.007). In addition, the
continuous FNB group consumed fewer oral narcotics compared to the opioid-only group (23 mg
vs. 38 mg, p = 0.004 on POD 1, 38 mg vs. 45 mg on POD 2, p = 0.32). However, on POD 3, the
catheter group and control group had no statistically significant differences in oral narcotic
consumption (23 mg vs. 15 mg, p = 0.22). On POD 2, subjects in the FNB group had greater
knee flexion compared to the control group (90 degrees vs. 75 degrees, p = 0.004). However,
those in the FNB group had lower scores for self-positioning and ambulation without assistance
compared to the control group, which may have been related to motor weakness. Limitations of
this study include not having a large enough sample size to determine significant differences for
many of the long-term follow-up measurements like range of motion, current medication use,
and pain scores.
Continuous Peri-Articular Infiltration (CPAI)
In 2015, Ali et al. completed a randomized control trial of 100 patients that evaluated the
effects of CPAI with LA infusion compared to saline placebo infusion postoperatively in TKA
patients (See Table 3). Pain was measured by scores on the visual analog scale (VAS) (0 mm =
no pain; 100 mm = severe pain) twice daily, and total opioid consumption was recorded twice
daily at 12 pm and 8 pm for 3 days, using oxycodone 5 mg. Both treatment groups received
spinal and general anesthesia for intraoperative anesthesia. A postoperative articular infusion,
administered thought an Elastomeric© infusion pump, was connected to a catheter placed in the
knee joint. Postoperative opioid pain medications were administered PRN and consisted of
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oxycodone 5mg. Group one consisted of patients who received a CPAI of ropivacaine 7.5
mg/ml, running at 2 mL/hr for 48 hr, and group two consisted of patients who received a CPAI
of normal saline. On postoperative day one, group one reported lower pain scores at 12 pm
(mean VAS = 33 mm) and 8 pm (mean VAS = 36 mm) compared to group two at 12 pm (mean
VAS = 40 mm) and 8 pm (mean VAS = 40 mm). On postoperative day two, group one reported
lower pain scores at 8 pm (VAS =27 mm) compared to group two at 8 pm (VAS=30 mm) (p=
0.02). Group one reported a lower mean total opioid consumption (oxycodone 4 mg) vs. group
two (oxycodone 5 mg) (p= 0.06). Adverse effects reported were higher incidence of surgical
wound infections in the CPAI treatment (11 surgical wound infections) compared to patients in
the control group (2 surgical wound infections) (p=0.02). The limitation to the study was that
pain scores were only recorded at rest and not during mobilization in order to allow for
standardization.
In 2016, DiFrancesco et al. investigated whether a combination of pain medication
[levobupivacaine 200 mg, ketoral-trometamina 30 mg, adrenalin 0.1 mg] delivered as a CPAI
(group A) when compared to a postoperative opioid regimen without surgical site infiltration
(group B) would decrease pain postoperatively in TKA patients. In this randomized control trial,
all 55 patients underwent spinal anesthesia for the procedure, and pain as measured as mean
VAS pain scores (0 – 100 mm where 0 was no pain and 100 was intolerable pain) (24 hr, 48 hr,
72 hr), as well as opioid consumption, reported as mg morphine. The spinal was performed with
10-15 mg of bupivacaine 0.75% or 0.5% and fentanyl 20 mcg. All patients were sedated
intraoperatively with intravenous midazolam and propofol titrated by the anesthesiologist. The
periarticular catheter was placed into the intra- and extra-articular subfascial space of the surgical
site at the end of surgery for local anesthetic infusion. Both groups used the Painfursor catheter
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Baxter© pump as the default infusion pump. The patients in group one received 10 cc/h for the
first 30 hr and 5 cc/h for the subsequent time. Raw value VAS outcomes were reported with no
inferential statistics; therefore; we can say the values of group A compared to group B were
larger at rest, at 24 hr (mean VAS value 26 mm ± 3 vs. 46 ± 4), at 48 hr (mean VAS value 10
mm ± 5 vs. mean VAS value 20 mm ± 6) and at 72 hr (mean VAS value of 0 mm vs. 11 mm ±
3). Mean pain VAS scores were decreased for the treatment groups at all hr marks during
mobilization at 24 hr (36 mm ± 4 mm vs. 45 mm ± 6) at 48 hr (18 mm ± 2 mm vs. 36 mm ± 4),
and at 72 hr (5 mm ± 1 mm vs. 24 mm ± 6 mm). Narcotic consumption of morphine
hydrochloride, measured by mean morphine administered (mg) for the treatment group vs. the
control group (5 ± 1 mm vs. 8 ± 1.2 mm), was also lower in the treatment groups. A limitation of
this study was the small sample size of only 55 patients.
In 2013, Williams et al. investigated the infusion of bupivacaine as a CPAI as a
postoperative pain modality in patients undergoing a TKA. A double-blind, randomized control
study consisted of group one (n=26) receiving a CPAI of 0.5% bupivacaine and group two
(n=25) receiving a placebo infusion of normal saline. The outcome measures were morphine
consumption (mg) and VAS pain scores (0 mm = no pain; 10 mm = severe pain). All patients
underwent spinal anesthesia with of plain bupivacaine 0.75% or 0.5% (10–15 mg) and fentanyl
20 mcg, with midazolam and propofol titrated intraoperatively. Both treatment groups used a
Stryker Pain© infusion pump at an infusion rate of 2 mL/hr for 48 hr. Both groups received the
same adjunct pain medication of ketorolac 7.5 mg IV preoperatively and 15 mg every 6 hr
postoperatively for 48 hr). After 48 hr, patients were switched to ketorolac tablets 10 mg every 6
hr for two days, gabapentin 600 mg preoperatively plus 300 mg twice daily for 48 hr
postoperatively, oxycodone 10 mg twice daily for 48 hr postoperative and acetaminophen tablets
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650 mg by mouth every 4 hr for 72 hr. Mean VAS scores in the first 6-8 hr were not different
between group one (2.4) vs. group two (3.1) (p=.428); at the 24 hr mark, group one (1.7) vs.
group two (2.1) (p=.386), and during the 48 hr mark, group one (1.4) vs. group two (1.8)
(p=.270). Morphine consumption in the control group (53 mg ± 30.4) and in the treatment group
(39 mg ± 27.1) were not statistically significantly different (p=.137). The research team opined
that the lack of significant difference in pain scores and morphine consumption between the two
groups was due to the inability to balance specific factors such as anesthetic type, procedure
variability, patient factors such as pain tolerance, and actual intervention potency. Limitations in
this study were the patient variabilities (weight and opioid tolerance) that potentially altered the
mean scores for opioid consumption.
In 2021, Fitz et al. investigated the efficacy of a CPAI catheter postoperatively for pain
control in patients undergoing TKA using spinal anesthesia and standard perioperative
management, as described below. Both groups underwent spinal anesthesia and received
intraoperative and postoperative pain regiments. Preoperatively patients received oral
medications which, were acetaminophen 925 mg and celecoxib 400 mg. Both groups received an
intraoperative, pericapsular injection of 49.25 mL ropivacaine (5 mg/mL), 0.8 ml clonidine (0.1
mg/mL), 0.5 ml epinephrine (1 mg/mL), and ketorolac 30 mg. In this randomized control study,
55 patients were divided into two groups and received either a CPAI catheter placed
intraoperatively in the surgical site after surgery, with a CPAI of 0.5% bupivacaine infusion at 2
ml/hr, versus no pain catheter in the control group. Outcomes were pain scores measured by a
VAS satisfaction survey (1 to 4 units with unavailable measurements defined), after initial
postoperative recovery and then after initial postoperative recovery and then every 4 hr and
opioid consumption (morphine milligram equivalents). Values reported, such as VAS and
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morphine milligram equivalents, were not clearly defined and should be cautiously interpreted.
Patients submitted a pain VAS score after initial recovery at baseline and then every 4 hr while
either awake or receiving pain medication. Pain scores and opioid consumption were reported
every 8 hr for the duration of a 48 hr period. The catheter was removed on postoperative day one,
approximately 24 hr after surgery. Before catheter removal, patients received 30 mL of 0.5%
bupivacaine through the catheter in the anterolateral suprapatellar space. Postoperative pain
regimens consisted of oral medications such as tramadol (50 mg 1-2 tabs TID), acetaminophen
(925 mg TID), gabapentin (600 mg QD), hydromorphone (1-2 mg oral for breakthrough), and
oxycodone (5 mg oral for breakthrough). Pain scores in the control group vs. the treatment group
were not significantly different for six time intervals during the 48 hr period: T1 (0-8 hr) 2.04 vs.
2.73 (p=.092), T2 (8-16 hr) 1.89 vs. 1.99 (p=.839); T3 (16-24 hr) 2.77 vs. 3.33 (p=.160); T4 (24-
32 hr) 2.97 vs. 3.25 (p=.620); T5 (32-40 hr) 2.89 vs. 2.56 (p=.641); T6 (40-48 hr) 2.34 vs. 2.72
(p=.431). Mean opioid consumption scores, measured in morphine mg equivalents, and the
results in the control group vs. the treatment group were not significantly different for each time
interval during the 48 hr period: T1 (0-8 hr) 6.77 mg vs. 9.54 mg (p=.210), T2 (8-16 hr) 8.42 mg
vs. 12.66 mg (p=.176); T3 (16-24 hr) 10.81 mg vs. 15.42 mg (p=.165); T4 (24-32 hr) 11.39 mg
vs. 13.56 mg (p=.566); T5 (32-40 hr) 12.24 mg vs. 13.50 mg (p=.718); T6 (40-48 hr) 12.76 mg
vs. 14.68 mg (p=.530). Mean opioid consumption was not statistically different between the
groups at any time. Limitations that existed were treatment by indication bias due to the lack of a
sham catheter. Fitz et al. reported this may have altered the mindset of the patient as well as
those in charge of care for the patient and could have been the reason for a trend in increased
opioid consumption in the treatment sham-catheter infusion group. Another limitation that
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existed was the small sample size which could have prevented the detection of statistically
significant data that was less than 1.1 on the mean VAS scores.
Goyal et al. (2013) conducted a double-blind, placebo-controlled, randomized-controlled
study investigating whether CPAI decreased patient postoperative pain scores and opioid
consumption. One hundred and fifty patients were randomized into two groups: the experimental
group that received 0.5% bupivacaine continuously at 5 mL/hr through an On-Q pump and the
control group that received 0.9% normal saline continuously at 5 mL/hr through an On-Q pump.
All patients received the same spinal anesthesia containing bupivacaine 12.5 mg and morphine
0.2 mg. After the TKA was cemented, the continuous catheter was placed in each patient before
the surgical dressing was applied. Investigators initiated the On-Q infusion pumps immediately
postoperatively in both groups. In addition, both groups received the same non-opioid
postoperative pain regimen of acetaminophen 650 mg every 6 hr, pregabalin 75 mg every 12 hr,
and IV ketorolac 30 mg every 6 hr. Both groups could request opioids for breakthrough pain,
including oxycodone 5-10 mg every 4 hr, hydrocodone 10 mg PO, codeine 10 mg PO,
hydromorphone 5 mg PO, hydromorphone 2 mg IV, fentanyl PCA 50 mcg IV, and tramadol 50
mg PO. Patients rated their current pain from the least pain in the past 12 hr and the most pain in
the last 12 hr using the VAS (0 mm = no pain; 100 mm = severe pain). The study found that the
average current, least, and most VAS pain scores were significantly lower in the CPAI group
compared to the normal saline group on POD 1 (POD 1 current 30.30 vs. 39.59, p = 0.015; POD
1 least 15.28 vs. 21.57, p = 0.032; POD 1 most 49.55 vs. 61.13, p = 0.013). In addition, pain
scores continued to trend lower in the experimental group compared to the control group POD 2,
which demonstrated clinical significance but not statistical significance (POD 2 current 19.30 vs.
24.19, p = 0.147; POD 2 least 12.34 vs. 15.39, p = 0.256; POD 2 most 40.85 vs. 49.87, p =
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0.048). Opioid consumption between the two groups was similar on POD 1 (11.73 vs. 11.84, p =
0.957). However, there was significantly less opioid consumption in the experimental CPAI
group on POD 2 and POD 3 (POD 2 6.69 vs. 9.96, p = 0.021; POD 3 4.0 vs. 8.7, p = 0.038).
Limitations of this study include not being able to control the duration of action of the
intraoperative spinal anesthesia or control the potential pain-inducing stimulating factors before
and after obtaining VAS scores. In addition, the study did not have a large enough sample size to
investigate changes in infection rate. However, this was not a primary outcome measure of the
study.
For completeness, a meta-analysis conducted by Sun et al. (2015) was included, which
compiled 10 RCTs that investigated CPAIs against saline placebo infiltrations in patients who
underwent primary TKA. Of the compiled RCTs within the meta-analysis, reported outcomes
included at least one of the following: postoperative VAS pain scores (with rest and during
mobilization), the incidence of infection, surgery time, and length of surgery. Of note,
heterogeneity existed among the included RCTs definition of VAS. The inclusion of this meta-
analysis is beneficial because several of the articles fall outside the defined time interval of this
literature review (before 2011) but fully fit all other methods of search criteria for inclusion.
Within 8 RCTs, totaling 511 patients, VAS pain scores were reported at rest. Comparing CPAI
and saline placebo infusions, CPAI provided better pain relief than placebo controls at 24 hr
during rest (Mean difference (MD) in VAS scores -12.54, p < 0.000001), while there was no
statistical difference between mean VAS scores during rest at 48 hr (MD -6.15, p = 0.10) and 72
hr (MD -3.63, p = 0.29). Within 5 RCTs, totaling 350 patients, VAS pain scores were reported
during mobilization. Continuous periarticular infiltration showed beneficial pain relief (as
represented by lower VAS pain scores) when compared to saline infusion during mobilization at
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24 hr (MD -18.27, p = 0.0001) and 48 hr (MD -14.19, p = 0.0001). There was no statistical
difference at 72 hr (MD -0.91, p = 0.62). Of clinical importance to this literature review,
evidence appears to support an increased incidence of catheter-related infections with the CPAI
technique. Within 7 RCTs, totaling 290 patients, infection occurrences were statistically
significant, as represented by risk ratios (RR) (RR 3.16, p = 0.02). However, Sun et al. (2015)
believe that this statistical conclusion was skewed by one research investigation conducted by
Ali et al. (2015) (as detailed above). When excluding the Ali et al. investigation from the
statistical analysis, there is no statistically significant difference in infection occurrences between
the CPAI and saline placebo groups (6 RCTs, 193 patients: RR and p-value note reported).
Investigations Comparing CPNB and CPAI for TKA Analgesia
In a single-center, double-blinded trial comparing the effectiveness of intra-articular
catheter infusions (CPAI) and continuous FNBs (CPNB) in providing postoperative analgesia for
cruciate retaining TKA procedures, 50 patients were randomized into two respective intervention
groups (Stathellis et al., 2015) (see Table 4). Other than the randomized catheter technique
interventions, all patients received identical intraoperative (general anesthesia) and postoperative
analgesic medication (ibuprofen + PRN opioids) regimens. The CPAI intervention group
received a pericapsular injection (containing bupivacaine 0.5%, epinephrine 0.0005%,
ketoprofen 100 mg, and morphine 10 mg) subcutaneously and into the capsule before incision
and before wound closure, followed by insertion of a 19 G, 60 cm long, intra-articular catheter
advanced into the medial gutter with 0.25% ropivacaine infusing at 5ml/hr. The CPNB
intervention group received a single-shot sciatic nerve block (20 ml 0.75% ropivacaine) and had
a femoral nerve catheter inserted 30 min before surgery with 0.75% ropivacaine at an infusion
rate of 10 ml/hr (with infusion reduction to 5 ml/hr on POD 2-3). The average indwelling
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catheter duration was four days for both intervention groups. The mean overall visual analog
score (VAS, measure of perceived pain intensity on a linear scale of 0 – 10 cm) for postoperative
pain was lower for patients who received CPAI (vs. CPNB) with significant reductions at 24 hr
(3.7 cm vs. 6.7 cm, p < .001), 72 hr (2.6 cm vs. 4.1 cm, p = .036), and 96 hr (2.3 cm vs. 4.9 cm, p
< .001). Additionally, there was an observed increase in VAS pain scores after removing the
catheter in the CPNB group that was not experienced by the CPAI group. The authors
commented that this was one of the more important findings of the research, because it could
indicate that interrupting afferent fibers at the site of nociceptive signal generation (rather than
more proximally along the neuronal pathway; CPNB) could offer additional protective
mechanisms against pain generation. Mean additional opioid consumption, measured by mean
morphine milligram equivalents (MMEs), was calculated for the entire postoperative period. The
CPAI group utilized significantly less opioids than the CPNB group (42.3 vs. 88.0 mg, p = .04).
There were no statistically relevant differences in passive knee flexion and Knee Society Scores
(KSS—a validated objective scoring system that reflects knee joint function by measuring
alignment, instability, joint motion, and symptomatology). However, the CPAI group
demonstrated a statistically significant ability to elevate the operative leg when the CPNB group
could not, at all postoperative time intervals (1 hr, p < .001; 3 hr, p < .001; 6 hr, p < .001; 24 hr,
p < .001; 48 hr, p <.001; 3 days, p = .002; 4 days, p = .005; 5 days, p = .012) except POD 6.
There were no patient falls in the CPAI group and two patients fell in the CPNB group. The
authors of this study hypothesized that the recorded increased fall occurrences in the CPNB
group could be attributed to exacerbated femoral nerve palsy and quadriceps weakness (well-
documented adverse effects of these blocks) with continuous dosing leading to accumulation of
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LAs. Otherwise, there were no other complications noted. Additionally, only one surgeon
conducted all TKA procedures in this study.
In 2017, Zinkus et al. also conducted a single-center prospective randomized control trial
comparing the efficacy of CPNB and CPAI in providing adequate and prolonged postoperative
analgesia within a 54-patient unilateral TKA population. “Group F” (CPNB) received an
ultrasound-guided 3-in-1 femoral nerve catheter for administering a mixture solution of 0.125%
levobupivacaine and 5 ug/ml fentanyl at a rate of 7-12 ml/hr for 72 hr postoperatively. “Group I”
(CPAI) received an intra-articular catheter infusing capsules, ligaments, tendons, and soft tissues
of the knee joint. An infusion of a mixed solution containing 0.125% bupivacaine (50 ml) and
5 ug/ml fentanyl was administered at a rate of 7-12 ml/hr for 72 hr postoperatively. Other than
the two intervention groups described, the intraoperative spinal anesthesia and the postoperative
analgesic regimen remained consistent between the two groups, which included: patient-
controlled analgesia infusion (PCA) morphine, diclofenac, and acetaminophen for 72 hr.
Although there were no statistically significant differences in VAS pain scores
(scores 0 – 100 mm) when measured pre- and postoperatively between the two interventions
(p > .05), the CPAI group had lower postoperative opioid use (as measured by MMEs) within the
first 24 hr (4.89 vs. 8.56; p = .033) compared to the CPNB group; opioid consumption measured
24- and 48 hr post-op revealed no difference between groups. Utilizing the Bromage Motor
Blockade Score (BMBS), which is a valid and reliable method for assessing the onset and
progression of motor blockade by recording the patient's ability to move their lower extremities,
the CPAI group had statistically significantly lower scores throughout the entire 72 hr
postoperative measurement period (p < .05) indicating superior motor function over the CPNB
intervention. Neither intervention group reported adverse events.
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In the most recent study comparing the efficacy of indwelling catheter infusions to
peripheral nerves vs. articular cavities, Lutzner et al. (2019) conducted a single-center
prospective randomized control trial that investigated the analgesia and residual knee function
outcomes in 140 TKA patients who were in one of the following two groups. “Group R” (CPNB)
which received ultrasound-guided continuous infusions of 0.5% ropivacaine to the femoral nerve
and, through a separate catheter, 0.5% ropivacaine infusion to the sciatic nerve. Both infusions
were administered postoperatively at a 6 ml/hr infusion rate. Additionally, the CPNB group
received an intraoperative single shot block to the obturator nerve with 10 ml of 0.5%
ropivacaine. “Group L” (CPAI) received an intra-articular infusion of 0.2% ropivacaine to the
ligaments, periosteum, and fat pads in the open surgical site. A total of 400 ml of 0.2%
ropivacaine was infused into the articular space between intraoperative application and
postoperative infusion at a rate of 8 ml/hr for 44 hr. Rescue opioid analgesia was available to
both groups for three days postoperatively via PCA (intravenous) pumps and orally dosed PRN
oxycodone. The primary outcomes of this study included pain, as measured by a numeric rating
scale (NRS) during rest and movement (0 = no pain – 10 = most conceivable pain), and the
amount of rescue medication used by patients as measured by electronic medical records and
recorded in mg. Piritramide a synthetic opioid related to meperidine structurally, and used in
European countries, was used (Hinrichs et al., 2017). The analgesia and recovery outcomes were
investigated prospectively in the morning and evening of each POD (POD 1 through POD 7),
and at 3-months and 1-year. Pain ratings were statistically significant between the two groups on
the day of surgery (mean NRS 3.0 vs. 4.2, p = 0.037) and POD 1 (mean NRS 3.4 vs. 4.4,
p = 0.015), with the CPNB group being lower. There were no differences between pain at rest
after POD 1 or during movement throughout the entire postoperative period, including at the 3-
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month and 1-year time markers. In terms of rescue analgesia, the CPNB group needed
significantly less PCA pump-administered opioid analgesia on POD 1 (22.7 mg vs. 35.3 mg, p =
0.001) and POD 2 (15.2 mg vs. 24.1 mg, p = 0.009). Of note, the CPNB group needed
significantly more preoperative preparation time (56.6 min vs. 19.7 min, p < .001), but the CPAI
group needed more intraoperative time (124.8 min vs. 118.1 min, p = .013). The CPNB
experienced prolonged motor blockade longer than POD 3 in 15.3% of the study group vs. 1.5%
in the CPAI group (p = .01); independent walking was possible on POD 2 in a higher percentage
of the CPAI group (56% vs. 44%, p = .037). In terms of reported complications for the two
interventions, the CPNB group experienced a higher incidence of catheter-related complications,
including dislocation and leakage (11.4% vs. 1.4%, p = .017); two prosthetic infections, two
superficial wound revisions, one hematoma, and four patients with restricted ROM required
manipulation under anesthesia in the CPNB group. Two patients with restricted ROM required
manipulation under anesthesia in the CPAI group, one experienced wound dehiscence after a
fall, and one required removal of a fixed drainage. There were no statistically significant
differences in knee function or patient satisfaction. A noteworthy limitation of this study is that
the CPNB group had a significantly higher prevalence of comorbidities than the CPAI group,
which could have altered the results of measured mobility outcomes.

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Chapter 4
Results
The patient undergoing TKA requires great consideration when choosing pain
management techniques that provide effective and prolonged analgesia, enhance the opioid-
sparing approach, and have the lowest complication rates. This capstone paper aimed to enrich
the understanding of the efficacy and safety of local anesthetics administered through continuous
indwelling catheters.
To meet specific aim one, the authors performed an extensive literature review on studies
that investigated CPNBs compared to opioids, CPAIs compared to opioids, and studies that
compared CPNB to CPAI. The database search included: PubMed, Embase, Scopus, and Web of
Science. Most useful studies were retrieved from the PubMed database while applying the
snowballing technique. The search process was challenging because of the inconsistent
nomenclature used to describe indwelling catheter-based techniques of PNB and PAI.
Additionally, the numerous surgeon-specific techniques for TKA, the wide range of available LA
formulations, variations in targeted nerves for PNB, and abundant differences in the infiltration
locations for PAI fundamentally made synthesizing the summarized evidence difficult. The
aforementioned barriers to synthesis were further complicated by the wide range of methods
used throughout the literature for measuring efficacy and safety outcomes. Studies investigating
CPNB approaches included a total of 6 RCTs. Studies investigating CPAI approaches included 8
RCTs. The quality of the investigations was assessed as robust in most cases by this research
team because of randomization, purposeful control of confounding surgical variables (TKA
approach, unilateral TKA, etc.), satisfactory sample sizes (per power analyses), and consistency
among study group characteristics (age, gender, comorbidities) and uniformity with the use of
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additional analgesia interventions adjunct to the techniques of focus (benevolent use of adjunct
multimodal analgesia). When considering the multimodal analgesic environment of current
surgical practices - a major challenge that investigators face is deciphering the effects of one
analgesic technique with the possibility of confounding effects from several other incorporated
techniques (MMA Protocols).
To satisfy specific aim two, the authors synthesized an executive summary of the
evidence. This summary aims to serve as a resource for pain management providers to make
evidence-based selections of opioid-sparing analgesic techniques.
Summary of CPNB when Compared to Standard Postoperative Opioid Use
In all three studies focusing on continuous PNBs, the technique demonstrated lower
reported pain scores and opioid consumption in general compared to the control groups that
received opioid medication as needed (Hanson et al., 2014; Leung et al., 2018; Nader et al.,
2012). More specifically, Hanson et al. (2014) and Leung et al. (2018) found that patients
reported lower pain scores and required less opioids in the later postoperative time intervals,
which demonstrates the efficacy of continuous PNBs in prolonging the duration of analgesia.
Although the evidence confirming continuous PNB is strong, each of the three articles utilized in
this systematic literature review has limitations. Nader et al. (2012) was not a placebo-controlled
or double-blinded study. The patients in the control group knew they were only receiving opioid
analgesia and the intervention group knew they were receiving continuous femoral nerve
analgesia. According to the National Institute of Health (NIH) (2020), the gold standard for
evaluating interventions is through randomized, placebo-controlled studies, so the evidence
provided by Nader et al. seems to be a lower level of evidence than the other two studies.
Outside of decreased pain scores and prolonged duration of analgesia, Nader et al. (2012) also
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found no difference in length of stay between two groups, but 4 of 31 participants in the opioid
analgesia group had deep venous thrombosis or pulmonary embolism compared to 0 of 31
subjects in the continuous femoral block group, which was statistically significant, p = 0.04.
Hanson et al. (2014) found a 40% decline in quadricep strength in both control and intervention
group, but by POD 2, quadricep strength was greater in those who received the adductor canal
block version of a CPNB. Leung et al. (2018) studied hospital length of stay, ambulation
distance, and knee range of motion as secondary outcomes. They found no significant difference
in any of those outcomes besides range of motion was slightly greater POD 1 in the opioid
analgesia control group.
Summary of CPAI when Compared to Standard Postoperative Opioid Use
The existing research exploring the efficacy and safety of the addition of a CPAI to a
comprehensive MMA protocol, indicates there is minimal evidence to support its clinical
relevance in providing superior patient analgesia. In terms of measured pain scores and opioid
consumption, evidence consistently demonstrates that there is no improvement when CPAI is
incorporated (Ali et al., 2015; Fitz et al., 2020; Williams et al., 2012). However, two articles
reported surprisingly positive results with CPAI describing lower pain scores at rest, with
motion, and lower opioid consumption at 24 hr, 48 hr, and 72 hr (DiFrancesco et al., 2015 and
Goyal et al., 2013). Of note, the investigation by Ali et al. (2015) corroborated positive results
with reports of decreased VAS pain scores on POD 1, but at no other time. These positive
instances appear to be an anomaly compared to the preponderance of data. Regarding
complications associated with the CPAI technique, the control groups often received a placebo
(saline) CPAI, and few adverse effects were reported. In the sources reviewed, there was no
statistically significant difference with opioid-related side effects (nausea, vomiting, respiratory
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compromise, etc.), lower extremity ROM, ability to achieve straight leg raise, and length of
hospital stay. (Ali et al., 2015; Fitz et al., 2020; Williams et al., 2012). It is important to note that
DiFrancesco (2015) reported two instances of superficial wound infection in the CPAI group and
a single case of deep vein thrombosis and pulmonary embolism in the saline placebo group.
Additionally, Ali et al. (2015) reported a disproportionate number of postoperative wound
infections in the CPAI group (11/97) compared to the saline placebo group (2/95), which was
statistically significant (p < .02) and requires further follow-up studies. Goyal et al. (2013) also
reported three patients in each group returned to the operating room for manipulation under
anesthesia for stiffness, and one patient in each group for irrigation and debridement for infection
at the surgical site. Though the rates of patients having either complication were the same, the
study cohort was not large enough to truly investigate the rate of infection and muscle stiffness.
The results of the Sun et al. (2015) meta-analysis largely support the results of the articles
included in the above CPAI literature review, including a more comprehensive collection of
research articles (6 additional randomized control trials before 2011) which fell out of the scope
of this literature reviews methodology. Despite reviewing all available CPAI data the authors
were unable to conclude superiority of CPAI as a solution to providing prolonged analgesia in
TKA procedures. However, this meta-analysis reported efficacy with the CPAI method during
the 24-48 hr, particularly during mobilization and at 24 hr and during rest periods. Sun et al.
addressed the elevated infection result in the Ali et al. (2015) study as a statistical outlier (see
reported statistics in the literature review above, Section: Continuous Peri-Articular Infiltration
(CPAI)). They proposed that the finding is theoretically linked to prolonged infusions of LA
inhibiting local inflammatory mediators and multiple touch points during preparation of
numerous vials of LA for infusion pumps. In the preponderance of studies - CPAI, when
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compared to saline placebo, does not consistently provide superior postoperative analgesia or
decreased opioid consumption in patients who receive a multimodal analgesia protocol. This
evidence supports that the use of a CPAI may not yield improved patient outcomes when a
treatment protocol consists of a standard multimodal approach (Fitz et al., 2021; Sun et al., 2015)
Summary of CPNB Compared to CPAI
When analyzing the available research that exclusively compares the efficacy of CPNB to
CPAI, the evidence varies. There are instances of both interventions having evidence to support
their superiority in providing benefits and limiting complications. In terms of pain scores, results
varied indeterminately for analgesic efficacy between the two techniques comparing CPAI and
CPNB (Lutzner et al., 2020; Stathellis et al., 2015; Zinkus et al.,2017). In one of the three articles
reviewed, CPNB showed clear superioriority over CPAI in decreasing overall opioid
consumption during the first 48 hr postoperatively (Lutzner et al., 2020). CPAI, when compared
to CPNB, clearly demonstrated better outcomes, including the benefit that patients had an
increased ability to elevate the surgical extremity (Stathellis et al., 2015), associated with less
motor block with improved motor function (Lutzner et al., 2020; Zinkus et al.,2017), and an
increased incidence of being able to walk independently sooner in the recovery period (Lutzner
et al., 2020). Increased complications in the CPNB group was consistent across all three studies,
with a higher incidence of falls (Stathellis et al., 2015) and a higher incidence of catheter-related
complications, including dislocation and leakage (Lutzner et al., 2020). In summary, it is not
obvious which indwelling peripheral catheter for the infusion of local anesthetics is superior to
the other in terms of pain scores; however, CPNB shows consistency in decreasing opioid
consumption more than CPAI. Furthermore, CPAI shows a greater ability than CPNB to avoid
an intense and prolonged motor block facilitating extremity movement and rehabilitation.
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Additionally, CPNB may have a worse adverse event and complication profile. Additional
research, with well-designed trials and larger sample sizes, is needed to validate these findings.
Please see Table 5 – Summary of Results – for compilation of all literature articles found within
each subheading comparing CPNB and CPAI. Note: this table demonstrates the number of
articles that support each measurment listed. (page 74.)

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Chapter 5
Discussion
The authors anticipate the summaries presented in the Results sections will improve
postsurgical outcomes for the patient undergoing TKA by assisting anesthesia providers in
determining the superior option in prolonging analgesia, decreasing opioid consumption, and
minimizing catheter-related complications. The current investigation included an extensive
literature review of two catheter-based methods of providing postoperative analgesia for
orthopedic surgeries, focusing on TKA procedures. The challenge of postoperative analgesia in
this context includes the need for long-lasting analgesia, avoiding opioid drugs as possible, and
providing home care that does not require expert supervision since most of these procedures are
now conducted in the outpatient ambulatory surgery setting with early discharge home.
Furthermore, techniques chosen for this patient population should facilitate immediate
postoperative joint rehabilitation and mobilization to enhance patient outcomes while minimizing
complications. In regard to the critical 72 hr time period for needed analgesic effectiveness, in
this literature review the preponderance of evidence examined the time 24-48 hr post-op and not
the clinically relevant 72 hr period. Although the time periods are not synchronous, the nature of
each technique implies that its effects can be extended as long as necessary due to the use of a
continuous infusion.
As introduced above, the authors’ highlighted several limitations to investigating a topic
of this nature. Of particular importance is the lack of interventions with homogeneous
approaches, varying use of a wide variety of adjunctive analgesics, and widely varying study
design comparisons of heterogeneous patient groups in available articles supporting
recommendations and seeking consensus. Furthermore, the various practice cultures among
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hospital systems and geographical regions confound the already complicated methodology . The
lack of consistency within the orthopedic surgical specialty in approaches for TKA procedures
and the chosen pain management regimens has negative and confounding effects on the internal
and external validity and subsequent widespread application of the generated evidence.
The inconsistency begins with the numerous surgical approaches available for domestic
and international surgeons, which include the medial parapatellar approach, subvastus approach,
quadriceps-sparing approach, and several more (Zhao et al., 2021). In addition, the variations
found in patient specific MMA protocols further complicates comparing research methodologies.
With such a variety of techniques and numerous pharmacodynamic profiles used to achieve
MMA - attributing effects to any one technique or drug is challenging.
It is clear from the research that CPNBs decrease pain scores and opioid consumption.
Real-world settings where TKAs are performed should be the lens in which CPNB practicality is
judged. As previously stated, there has been a shift from inpatient to outpatient ambulatory
surgery centers to fast-track care models for TKA patients requiring swift discharge to a home
environment. As a result, it is vital to choose anesthetic and analgesic plans that reflect the short
recovery time allowed at these centers. The height of postoperative pain in TKAs is within the
first 72 hr, so if the intention is to prolong analgesic duration until then, home use of CPNBs
should be considered. At present time, home care is feasible, because patients can take home
portable infusion pumps - Monahan & Ilfeld (2022) state that electronic pumps are some of the
safest and most accurate methods of administering medications. However, there is still a learning
curve for the pumps, as streamlined as they are. Monahan & Ilfeld (2022) emphasize the
importance of patient education when dealing with these infusion pumps. Patients must learn
how to properly use the pumps and care for their catheter insertion site. If not taken care of
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properly, the insertion site can be an infection risk. Experts also recommend having a caregiver
participate in the education, as well, to support the patient in their learning and care. Utilizing an
at-home pump, while in theory is helpful to prolong the duration of analgesia, brings up a whole
host of issues like health literacy and access to resources like caregivers, the need for visiting
home health providers, and available time to dedicate to care.
Continuous periarticular infiltrations may be a viable option for pain relief in a patient
population where many of the major components of a MMA are contraindicated, but overall,
CPAI does not demonstrate superior patient analgesia. Although not superior, CPAI has some
comparable results to CPNB in terms of prolonged analgesia but with better side effect profiles,
which may be factored into the decision-making process by providers when choosing analgesic
methods. Continuous periarticular infiltrations clinical indications may not outweigh the risks in
a patient that can receive the same benefits from other systemic opioid sparing options such as
CPBN; however, CPAI may present lower risks for complications in patient populations who
have concomitant contraindications in receiving multiple systemic formulations of analgesia.
The CPAI modality may have other benefits that are not specific to pain but beneficial to patients
with contraindications for a multimodal approach of NSAIDS, oxycodone, gabapentin, or
acetaminophen. If a patient specific multimodal approach is a viable option then CPAI is not
warranted and may lead to various adverse effects, such as wound infections.
The unusual wound infections reported by Ali et al. (2015) (11 surgical wound infections
in the treatment group receiving a CPAI catheter vs. two surgical wound infections in the control
group who received a catheter infusing normal saline) were possibly due to the preparation of the
drugs used in the analgesic infiltration. Wound infections are only prevalent in the study by Ali
et al. The treatment group required the reintroduction of a syringe five times during pump
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preparation compared to the control group, which did not require any needle introduction. This
could have contributed to a break in sterility and caused contamination in the study group
because, typically CPAI technique results in lower infection rates and risk factors (Di Francesco,
2016; Williams, 2013; Fitz, 2021). However, in response to the possibility of increased infection
risk with the CPAI approach, the technique should be used with caution in patient populations
more predisposed to this complication, specifically in patients with a past medical history of
diabetes mellitus, liver disease, obesity, advanced age, and prolonged hospital stays (Noailles et
al., 2016).
Continuous periarticular infiltration is not the superior choice in reducing postoperative
pain and opioid consumption when compared to postoperative opioids alone. Continuos
periarticular infiltration is the inferior choice when the ability to use multimodal analgesia is
possible. Continuous periarticular infiltration is the superior choice when patient
contraindications limit the ability to use multimodal analgesia of opioids in the postoperative
period.
Peripheral nerve blocks and PAIs have been established throughout the literature as
effective analgesic techniques and proven to be valuable options for the current MMA
environment (Gabriel et al., 2019; Gaukhman et al., 2020; Seangleulur et al., 2016; Rodriguez-
Patarroyo et al., 2021). Furthermore, these techniques have been revised to be continuous
applications as a means of prolonging analgesia, which has instances of evidence to support the
efficacy of each of their applications separately (see Table 4 literature summary). When
considering the available research that directly investigates the efficacy and safety of CPNB
compared to CPAI, it is sparse and lacks outstanding generalizable evidence. Despite the
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ambiguous nature of the evidence, this research team believes there is value in several of the
conclusions revealed in this paper.
First, CPNB seems to have slight superiority over CPAI in providing analgesia and
decreased opioid consumption but may produce worse conditions for rehabilitation related to
increased muscle weakness. An important secondary outcome of this investigation has been
revealing the propensity for traditional FNB to produce quadriceps weakness, which may be
partially ameliorated by using an adductor canal block approach to FNB (Wang et al., 2017).
Wang et al., through a meta-analysis of 12 RCTs investigating adductor canal block and FNB
approaches, yielded objectively increased quadriceps strength and ability to ambulate while
maintaining statistically equivalent pain coverage and opioid requirements (2017). For this
reason, it may be prudent to only utilize the CPNB technique as a means of avoiding opioids in
patient populations with higher functional reserves and baseline lower extremity mobility. In the
context of at-home management, CPNB may be recommended only to patients with sufficient
resources and available support systems for identifying complications, preventing falls, and/or
poor rehabilitation progression.
Second, CPAI seems to have less profound analgesia effects when incorporated within a
comprehensive MMA protocol but provides a superior safety profile compared to CPNB. For
this reason, it may be reasonable to consider using the CPAI technique when patient-specific
circumstances contraindicate the use of one or more multimodal adjuncts (such as non-steroidal
anti-inflammatory drugs (NSAIDs), acetaminophen, gabapentin, peripheral nerve block, etc.).
More research, particularly with the utilization of a methodology that isolates CPAI from a
multimodal approach, is needed to validate this point. When focusing on the ambulatory setting
and same-day discharge TKA procedures, the ability of CPAI to avoid muscle weakness has
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critical utility. Indeed, in elderly and particularly infirm patient populations with an elevated fall
risk, CPNB may not be the best choice, as the associated risk of motor blockade may elevate the
risk of a fall with potentially catastrophic implications.
The important takeaway is that there is preliminary evidence for the utility of each of
these indwelling catheter techniques that can be applied to patient-specific circumstances. The
paper provides evidence to clinicians to help guide the selection of individualized and efficacious
pain management strategies. Undeniably, more high-quality randomized control trials with
improved standardization of methodology are necessary for a more rigorous comparison of
CPNA and CPAI. Moreover, it should be noted that catheter-based techniques will always have
the inherent disadvantage of increased risk for patient complications and strain on provider and
institution resources. For this reason, future research should explore novel local anesthetic
formulations and catheter-free applications with a primary focus of providing effective and
prolonged analgesia for orthopedic procedures such as TKA.
Such catheter-free applications of local anesthetics have been introduced to the market as
potential solutions for complication-free postoperative analgesia, such as SABER ® Bupivacaine
and HTX-011 (Zynrelef ®). At present, both novel formulations, which utilize proprietary
sustained-release technologies, have promising results for prolonged analgesia and demonstrate
promising safety profiles (Balocco et al., 2018). However, the current evidence to support these
preliminary claims has been funded and executed by the pharmaceutical companies responsible
for the genesis of the formulations, so providers should exercise caution with interpretation and
application. Zynrelef is currently the only formulation with evidence to support its use in TKA
procedures. Zynrelef, with recent FDA approval in May of 2021, utilizes a proprietary
bioerodible polymer (Biochronomer) that releases bupivacaine, a local anesthetic, and low-dose
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meloxicam, a non-steroidal anti-inflammatory drug (NSAID) to accomplish extended duration of
action (Lachiewicz et al., 2021). It is a topical medication applied directly to the surgical wound
site before closing the surgical site, allowing for a needle-free administration. Current research
indicates that the formulation may have a unique extended-release period exceeding 72 hr, which
is longer than the duration of the currently available LAs (Heron Therapeutics, 2021).
The expected and natural inflammatory response to tissue injury during surgical
intervention has a deleterious effect on the efficacy of local anesthetics related to the ionization
of local anesthetic before it can reach the effect site (Hargreaves & Keiser, 2002). The addition
of meloxicam stabilizes the wound bed, controls inflammation locally, and augments the efficacy
of bupivacaine by regulating the pH of the wound bed (Lachiewicz et al., 2021). Zynrelef has
shown promising results in bunionectomies, herniorrhaphy, and total knee arthroplasties by
effectively increasing pain relief while reducing opioid use (Goudra et al., 2021).
If Zynrelef is consistently proven effective, easily executed, and as safe as the current
research potentiates, how will future applications change the landscape of postoperative pain
management in the context of multimodal analgesia? Firstly, it will have synonymous
implications to the ones described for CPAI, mainly to provide a means of prolonged analgesia
while avoiding the complications of the motor block associated with CPNB. The ambulatory
surgical arena will globally benefit, as described above. Secondly, due to the nature of Zynrelef’s
needle-free application, it has the potential to avoid the array of complications that comes with
maintaining an indwelling catheter for prolonged periods. Thirdly, the simplicity of Zynrelef’s
application technique may also avoid the additional resources and technical skill sets required to
place PNBs and the indwelling catheters needed for CPNB/CPAI. This particular benefit of the
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needle-free application has a significant upside for healthcare settings with limited resources,
such as critical access hospitals in rural locations and various austere environments.
In conclusion, this investigation has explored the analgesic efficacy of two catheter-
related approaches to providing long-lasting pain relief for TKA procedures. This investigation
compared the advantages and disadvantages of each technique with each other and traditional
opioid-based analgesia. This research team found that the catheter-based approaches of using
local anesthetics in prolonged infusions can, indeed, supply effective analgesia for this patient
population, thus decreasing the use of opioid analgesics and the complications associated with
opioid use. Each technique has low complication rates; notably, the risk of quadriceps muscle
weakness is higher with CPNB. As with all anesthesia approaches, a thorough preoperative
examination, and grasp of the pharmacology and techniques necessary, will aid anesthesia
providers in selecting which technique offers the greatest safety and utility suited to individual
patient needs.

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Figures

Figure 1
The Challenges of Postoperative Pain Management with TKA.

Note: This figure visually demonstrates the duration of analgesia each intervention provides.
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METHODS TO PROLONG POSTOP ANALGESIA IN TKAS

Figure 2
PRISMA 2022 flow diagram for the systematic review of CPNB and CPAI

Note. This figure provides details of the search process for evidence supporting this study.

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METHODS TO PROLONG POSTOP ANALGESIA IN TKAS

Tables
Table 1
Glossary of Operational Terms
Term (Abbreviation) Definition
Continuous
Periarticular
Injection (CPAI)
The continuous infiltration (installation) of a mixture of
formulations, through an indwelling catheter, directly into and
around the surgical field (articulation) to intercept the generation
of pain signals at the source of insult (Kerr & Kohan, 2008).

Continuous
Peripheral Nerve
Block (CPNB)
Continuous infusion of local anesthetics at peripheral nerves, via
indwelling catheter, to prolong anesthetic effects (Monahan &
Ilfeld et al., 2022).

Periarticular
Injection (PAI)

A single (one-time) injection of a mixture of formulations directly into
and around the surgical field (articulation) to intercept the generation
of pain signals at the source of insult (Kerr & Kohan, 2008).

Peripheral Nerve
Block (PNB) -
“Single Shot”
A single (one-time) injection of an analgesic medication into an area
that is highly innervated to provide pain management to a limb or area
of the body (Monahan & Ilfeld et al., 2022).

Local Anesthetics
(LA)
Local anesthetics are a group of drugs that inhibit the generation and
conduction of nerve impulses by blocking sodium ions from entering
the sodium voltage-gated channels (Monahan & Ilfeld et al., 2022).

Total Knee
Arthroplasty (TKA)
Knee Replacement Surgery: is a surgical procedure to resurface a knee
damaged by arthritis. Metal and plastic parts are used to cap the ends
of the bones that form the knee joint. (Johns Hopkins Health System,
n.d.).
Note. This table explains and defines the technical terminology used in this paper.
METHODS TO PROLONG POSTOP ANALGESIA IN TKA PROCEDURES

70
Table 2
Literature Review: CPNB

Article Intervention
Groups
Type of
Anesthesia
Intervention Local Anesthetic
Used
Rate of
infusion
Additional Postoperative
Analgesia (MMA)
Pain Scores Opioid Consumption
Hanson et
al. (2014)
(n = 80)
CPNB

Vs.

CPNB
Saline
Placebo +
Postop PRN
Opioids
Moderate
Sedation
(Propofol
Infusion)
Adductor Canal
Block
0.2% Ropivacaine 8 mL/hr of
0.2%
No additional postoperative
analgesia regimen detailed in
study.
Resting Numeric Rating Scale (NRS) was
measured at 6 hr intervals.

NRS scores were significantly lower at 18hr
and 30 hr in the block group.
Mean morphine consumption
was lower in the adductor canal
block group than the sham
group.

The adductor canal block group
continued to demonstrate lower
opioid consumption 24-48 hr
after the presumed resolution of
a single-shot femoral nerve
block.
Leung et al.
(2018)
(n = 76)
CPNB

Vs.

CPNB
Saline
Placebo +
Postop PRN
Opioids
Neuraxial
Anesthesia
(Epidural
or CSE*)
Adductor Canal
Block
0.125%
Bupivacaine
8 mL/hr Morphine 1-2 mg IV PRN
Oxycodone XR 10 mg PO BID
Tramadol 50 mg IV Q6 hr
Hydrocodone/acetaminophen 5-
325 mg PO Q4-6 hr PRN
Visual Analog Scale (VAS) (0-10)

There was a significant decrease in VAS score
in the block group 20 hr after catheter
placement.
No difference in morphine
consumption between the two
groups at 12 hr (epidural still in
place).

However, at 20 hr post-op, the
sham catheter group required
significantly more morphine
than the block group.
Nader et al.
(2012)
(n = 62)
CPNB

Vs.

Opioids
Epidural
Anesthesia
Femoral Nerve
Block
0.25%
Bupivacaine and
0.1% Ropivacaine
5 mL/hr Hydrocodone 10 mg PO q4-6 hr
PRN
Acetaminophen 625 mg PO q4-6
hr PRN
If Verbal Rating Score for Pain
(VRSP) (0-10) scores weren’t
lower than 4, switch to
Hydromorphone 2 mg PO q4 hr
PRN and extended-release
Oxycodone 10 mg PO q12 hr PRN
There was a significant decrease in VRSP in
the femoral block group compared to the
opioid group after discontinuation of the
epidural anesthesia 24 hr post-op
There was a significant decrease
in opioid consumption in the
femoral block group 24 hr post-
op.

Note. This table provides data for studies of CPNB management of postoperative analgesia for TKA procedures. *CSE
= Combined Spinal Epidural.

METHODS TO PROLONG POSTOP ANALGESIA IN TKA PROCEDURES

71
Table 3
Literature Review: CPAI

Article Intervention
Groups
Type of
Anesthesia
Local Anesthetic
Used
Rate of
infusion
Additional Postoperative Analgesia
(MMA)
Pain Scores Opioid Consumption
Ali et al.
(2015)
(n = 200)
CPAI

Vs.

CPAI Saline
Placebo
Spinal/
General
Anesthesia
Ropivacaine (200
mg; 2 mg/mL)
Ketorolac (30 mg;
30 mg/mL)
Epinephrine (0.5
mg; 0.1 mg/mL)
2 mL/h for
48 hr
Paracetamol 500 mg PO
Diclofenac 25 mg PO
Buprenorphine Patch 10 μg/h
(changed 1/week for a total of 3
weeks)
Oxycodone 5 mg PO PRN
VAS (0-100) at 12 p.m. & 8 p.m.
Pain at 24 hr, lower in CPAI group (p = 0.02)
VAS at 12 p.m. was 33 in the therapy group and 40
in the control group (p = 0.02);
Values at 8 p.m. were 36 and 43 (p = 0.03)
Patient Records of Opioid
Consumption

Total opioid consumption was less
in CPAI group (p=0.06)
DiFrancesco
et al. (2016)
(n = 70)
CPAI

Vs.

CPAI Saline
Placebo
Spinal
Anesthesia
Levobupivacaine
(200 mg),
Ketoral-
trometamina (30
mg),
Adrenalin (0.1mg)
10 ml/hr
for the first
30 h
5 ml/hr for
subsequent
Ketorolac 30 mg PO
(Max daily dose = 120 mg)
Morphine hydrochloride 5 mg SubQ.
Visual Analog Scale (VAS) (0 -100 mm) at 12 p.m.
& 8 p.m.

Pain levels were lower in the pain pump group at all
time levels at rest and during ROM (no inferential
statistics reported)
Narcotic consumption was lower in
the pain pump group during the
entire period of observation
Goyal et al.
(2013)
(n = 150)
CPAI

Vs.

CPAI Saline
Placebo
Spinal
Anesthesia
0.5% Bupivacaine 2 ml/hr for
48 hr
Acetaminophen 650 mg PO q6hr
Pregabalin 75 mg PO BID
Ketorolac 30 mg IV q6hr
Oxycodone 5-10 mg PO q4 PRN
Hydrocodone 10 mg PO PRN
Codeine 10 mg PO PRN
Hydromorphone 5 mg PO PRN
Hydromorphone 2mg IV PRN
Fentanyl PCA 50 mcg IV PRN
Tramadol 50 mg PO PRN
VAS pain scores significantly different for the
average highest, current, and lowest scores POD 1.
VAS scores POD 2 were lower in the CPAI group
compared to the control group, but not statistically
significant.
There was no difference in opioid
consumption POD 1 between the
two groups. However, there was
significantly less opioid
consumption on POD 2 and 3 in the
experimental group
Williams et
al. (2013)
(n = 51)
CPAI

Vs.

CPAI Saline
Placebo
Spinal
Anesthesia
0.5% Bupivacaine 2 ml/hr for
48 hr
Ketorolac 15 mg PO q 6hr
Gabapentin 300 mg PO BID
Oxycodone CR 10 mg PO BID
Acetaminophen 650 mg PO q4hr
Mean VAS pain scores were not different between
the bupivacaine and saline groups
6-8 hr mark (p < .428)
24 hr mark (p < .386)
48 hr mark (p < .270)
No difference in PCA morphine mg
equivalents consumed within the
first 48 hr postoperatively (p=.137)
Fitz et al.
(2021)
(n= 50)
CPAI

Vs.

CPAI Saline
Placebo
Spinal
Anesthesia
0.5% Bupivacaine 2 ml/hr for
48 hr
Tramadol 50 mg PO TID
Acetaminophen 925 mg PO TID
Gabapentin 600 mg PO QD
Hydromorphone 1-2 mg PO
(For breakthrough)
Oxycodone 5mg PO
(For breakthrough)
VAS pain scores were not statistically different (p >
.05) at all time-points to 48 hr
No statistical difference in
morphine consumed (p >.05)
between groups at any time-point

Note. This table provides data regarding the analgesic efficacy of CPAI approaches for postoperative analgesia for TKA procedures.
METHODS TO PROLONG POSTOP ANALGESIA IN TKA PROCEDURES

72
Table 4
Literature Review: Comparing CPNB and CPAI for Postoperative Analgesia in TKA Procedures
Article Intervention
Groups
Type of Anesthesia Intervention Local
Anesthetic
Used
Rate of infusion Additional
Postoperative
Analgesia (MMA)
Pain Scores Opioid Consumption
Lutzner et
al. (2020)
(n = 140)
CPNB General or Spinal
Anesthesia:
Based on total patient
picture, patient
preference, and
provider technique.
Continuous
Femoral Nerve Block
0.2%
Ropivacaine
6 ml /hr Novamine Sulfon1 1 g
PO q8 hr
Oxycodone 10 mg PO
q12 hr
Piritramid2 PCA pump
for 72 hr postop.
Numerical Rating Scale (NRS) (0-10)

Pain at rest, lower in CPNB group on
POD 0 and POD 1.

POD 0 (mean NRS 3.0 vs. 4.2, p =
0.037)
POD 1 (mean NRS 3.4 vs. 4.4,
p = 0.015)

Pain on subsequent PODs, at 3 months,
and 1 year = no difference.
Patient Records of Opioid
Consumption

Opioid consumption via PCIA
pump was less in CPNB group

POD 1(22.7 mg vs. 35.3 mg, p
= 0.001)

POD 2 (15.2 mg vs. 24.1 mg,
p = 0.009)
Single Shot Obturator
Nerve Block
0.5%
Ropivacaine
10 ml once
Continuous
Sciatic Nerve Block
(Separate catheter)
0.2%
Ropivacaine
6 ml /hr
CPAI Intra-articular block
within surgical site,
infiltration to:
capsules, tendons,
ligaments, soft tissue
0.2%
Ropivacaine
(400 ml total)
8 ml /hr
(44 hr total)
Stathellis
et al.
(2015)
(n = 50)
CPNB General Anesthesia Femoral Nerve Block
Continuous
0.75%
Ropivacaine
10 ml /hr
incrementally
decreased over
72-120 hr total.
No additional
postoperative analgesia
regimen detailed in
study—described as
“ibuprofen and PRN
opioids”.
Visual Analog Scale (VAS) (0-10 cm)
Pain at 24 hr, lower in CPAI group (3.7
cm vs. 6.7 cm, p < .001)

Increased pain (rebound pain) observed
in CPNB group after catheter removal.

POD 3, less pain in CPAI group (2.6 cm
vs. 4.1 cm, p = .036)

POD 4, less pain in CPAI group (2.3 cm
vs. 4.9 cm, p < .001)
Patient Records of Opioid
Consumption

Total opioid consumption was
less in CPAI group

42.3 mg vs. 88.0 mg (42.3 vs.
88.0 mg, p = 0.04)
Sciatic Nerve Block
Single Shot
0.75%
Ropivacaine
20 ml once
CPAI Intra-articular block
within surgical site,
infiltration to:
capsules, tendons,
ligaments, soft tissue
0.25%
Ropivacaine
5 ml /hr
Zinkus et
al. (2017)
(n = 54)
CPNB Spinal Anesthesia:
L2-L3 subarachnoid
with 0.5%
Levobupivacaine, 3 ml,
15 mg.
+ Propofol infusion 1-2
mg/kg/hr.
+ Capsular Infiltration
0.125% bupivacaine
40 ml, 50 mg
+ epinephrine 0.07 mg
3-in-1 femoral nerve
block
0.25%
Levobupivacai
ne + 5 ug/ml
Fentanyl
7-12 ml /hr
72 hr total
Morphine PCA pump
for 72 hr: 1 mg, 7 min
lockout.

Diclofenac PO 150 mg
q24 hr
Acetaminophen 1 g
q6 hr
Visual Analog Scale (VAS) (0-10)

There was no difference in pain scores
preoperative or postoperative during
rest, passive motion, active motion, and
walking.
Patient Records of Opioid
Consumption

Total Opioid consumption was
less in CPAI group

POD 0-1 (4.89 vs. 8.56; p =
.033)

No difference after POD 1
CPAI Intra-articular block
within surgical site
infiltration to
Capsules
Tendons
Ligaments
Soft tissue
0.125%
Bupivacaine
+ 0.2 mg
Epinephrine
+ 5 ug/ml
Fentanyl
120 ml total
7-12 ml /hr
72 hr total
METHODS TO PROLONG POSTOP ANALGESIA IN TKA PROCEDURES

73

Note. This table provides a comparison of the efficacy of CPNB and CPAI in providing postoperative analgesia for TKA procedures.
1. Novamine Sulfon is an amino acid injection that promotes protein synthesis and wound healing (Hinrichs et al., 2017).
2. Piritramide is a synthetic opioid structurally related to meperidine, and used in European countries (Hinrichs et al., 2017).
METHODS TO PROLONG POSTOP ANALGESIA IN TKA PROCEDURES

74
Table 5
Summary of Results
Measures of Benefits and
Limitations
Continuous Peripheral Nerve
Block (CPNB)
Continuous Periarticular
Injections (CPAI)
Decreased Opioid
Consumption

4 3
Decreased Pain Score

4 3
Notable Rebound Pain

1 --
a

Improved Functional Status

3 5
Surgical Wound Infection

1 2
Increased Fall Incidence

1 --
Catheter Dislodgement/
Leakage

1 --
Other Major Complications
(DVT/PE)

1 1
Increased Hospital LOS

-- --
Increased Time Utilization
(Preop)

1 --
Increased Time Utilization
(Intraop)
-- 1

METHODS TO PROLONG POSTOP ANALGESIA IN TKA PROCEDURES

75
Note. This table demonstrates the number of articles for each measurement in the comparison of the CPNB and CPAI. Please note,
only the first two measures are directly related to the specific aims of this investigation. Other measures are relevant secondary
outcomes that contribute to the discussion of technique efficacy and safety.
a
No Articles were found

Asset Metadata

Creator Pan, Joyce (author)

Core Title Comparison of continuous peripheral nerve block and continuous periarticular infiltration to prolong analgesia in total knee arthroplasty: an executive summary of evidence

Contributor Electronically uploaded by the author (provenance)

School Keck School of Medicine

Degree Doctor of Nurse Anesthesia Practice

Degree Program Nurse Anesthesiology

Degree Conferral Date 2024-05

Publication Date 08/28/2023

Defense Date 08/26/2023

Publisher Los Angeles, California (original), University of Southern California (original), University of Southern California. Libraries (digital)

Tag analgesia,catheter,continuous,indwelling,intra-articular injection,local infiltration,multimodal analgesia,OAI-PMH Harvest,opioid-sparing,periarticular infiltration,peripheral nerve block,total knee arthroplasty,wound infusion

Format theses (aat)

Language English

Advisor Bamgbose, Elizabeth (committee chair), Griffis, Charles (committee chair), Norris, Theresa (committee chair)

Creator Email joycep74@gmail.com,joycepan@usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-oUC113302372

Unique identifier UC113302372

Identifier etd-PanJoyce-12283.pdf (filename)

Legacy Identifier etd-PanJoyce-12283

Document Type Capstone project

Format theses (aat)

Rights Pan, Joyce

Internet Media Type application/pdf

Type texts

Source 20230830-usctheses-batch-1088 (batch), University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright.

Repository Name University of Southern California Digital Library

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Abstract (if available)

Abstract Total knee replacements (TKAs) are one of the most common but painful surgical procedures performed in the United States. Currently, the gold standard for postoperative pain management is the utilization of opioids. However, in the wake of the opioid epidemic, the healthcare system is attempting to reduce opioid consumption by trialing innovative opioid sparing techniques such as continuous peripheral nerve blocks (CPNB) and continuous periarticular infiltration (CPAI). Analgesia, particularly during the first 72 hr postoperatively, is vital due to its association with delayed recovery, impaired rehabilitation, immunosuppression, the development of chronic pain and rebound pain, and decreased patient satisfaction. While both techniques are being used today, there is limited evidence comparing them to the current standard of care or to each other. An extensive literature review was performed to explore the safety profiles and effectiveness of CPNB and CPAI in reducing pain scores and opioid consumption. The literature revealed the usage of CPNB contributed to lower pain scores and decreased opioid use when compared to opioid-only control groups. Additionally, CPAI did not improve pain scores or decrease opioid consumption when combined with a multimodal analgesic (MMA) regimen. When comparing CPNB and CPAI to each other, neither unanimously lowered pain scores, but the literature indicates that CPNB decreased opioid consumption more than CPAI. More research is needed to further cement the efficacy of CPNB and CPAI as standard components of MMA in TKA procedures. Future research can also focus on novel catheter-free applications to reduce the complications of continuous catheter analgesics.