Review Article

Current Strategies in Anesthesia

and Analgesia for Total Knee
Arthroplasty

Calin Stefan Moucha, MD
Mitchell C. Weiser, MD, MEng
Emily J. Levin, MD
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Abstract
Total knee arthroplasty is associated with substantial postoperative
pain that may impair mobility, reduce the ability to participate in
rehabilitation, lead to chronic pain, and reduce patient satisfaction.
Traditional general anesthesia with postoperative epidural and
patient-controlled opioid analgesia is associated with an undesirable
adverse-effect profile, including postoperative nausea and vomiting,
hypotension, urinary retention, respiratory depression, delirium, and
an increased infection rate. Multimodal anesthesia—incorporating
elements of preemptive analgesia, neuraxial perioperative anesthesia,
peripheral nerve blockade, periarticular injections, and multimodal oral
opioid and nonopioid medications during the perioperative and
postoperative periods—can provide superior pain control
while minimizing opioid-related adverse effects, improving patient
satisfaction, and reducing the risk of postoperative complications.

From the Department of Orthopaedic

Surgery (Dr. Moucha and Dr. Weiser)
and the Department of Anesthesiology
(Dr. Levin), Icahn School of Medicine at
Mount Sinai, New York, NY.
Dr. Moucha or an immediate family
member is a member of a speakers’
bureau or has made paid presentations
on behalf of 3M and serves as a board
member, owner, officer, or committee
member of the American Academy of
Orthopaedic Surgeons. Dr. Weiser
serves as a board member, owner,
officer, or committee member of the
American Academy of Orthopaedic
Surgeons. Neither of the following
authors nor any immediate family
member has received anything of value
from or has stock or stock options held
in a commercial company or institution
related directly or indirectly to the
subject of this article: Dr. Weiser and
Dr. Levin.
J Am Acad Orthop Surg 2016;24:
60-73
http://dx.doi.org/10.5435/
JAAOS-D-14-00259
Copyright 2016 by the American
Academy of Orthopaedic Surgeons.
T otal knee arthroplasty (TKA) is a
notoriously painful procedure.
This fact has prompted the study and
application of multimodal pain
modulation techniques to improve
patient satisfaction and outcomes.
Failure to control postoperative pain
has been associated with an increase
in sympathetic tone, causing vaso-
constriction and end-organ damage,
a decrease in intestinal motility,
increased nausea and vomiting, the
downregulation of immune function,
a delay in discharge, increased
healthcare costs, and potentiation of
chronic postoperative pain, leading
to chronic regional pain syndrome.1
Increasing evidence shows that the
types of anesthesia and analgesia
administered in the perioperative
period may affect the rates of surgical
site infection, urinary retention, ileus,
nausea and vomiting, and the
ability to safely participate in early
postoperative rehabilitation.2-12 The
American healthcare system is enter-
ing an era in which physician and
hospital compensation may be tied to
patient satisfaction and preventable
complications. The surgeon should
have an understanding of the current
anesthetic and analgesic options for
TKA as a basis for informed discus-
sions with patients and anesthesia
colleagues to better optimize patient
outcomes.
Multimodal Analgesia
Multimodal analgesia refers to the
combination of several types of med-
ications and delivery routes, including
peripheral nerve block (PNB), peri-
articular injection, patient-controlled
analgesia (PCA), and oral narcotic
and nonnarcotic medication. The
goal of multimodal analgesia is to
provide superior postoperative pain
control through the simultaneous

60 Journal of the American Academy of Orthopaedic Surgeons

Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.

modulation of several pain pathways
while minimizing the undesired
adverse effects of excessive narcotic
consumption, which can result in
nausea, vomiting, sedation, ileus,
respiratory depression, and pruritus.
Most multimodal protocols focus on
oral analgesics, which may be started
several days before surgery and usu-
ally are combined with oral opioids.
The ultimate goal is to provide ade-
quate pain relief without using intra-
venous opioids (Table 1).
Preemptive Analgesia
Preemptive analgesia begins before
surgery, with the goal of preventing
peripheral and central nervous sys-
tem sensitization secondary to the
surgical incision and surgical tissue
manipulation. The concept of pre-
emptive analgesia is based on
preventing the production of inflam-
matory chemicals during a painful
stimulus, thus avoiding the sensitiza-
tion of peripheral and central noci-
ceptors. The sensitization of these
nerve fibers lowers the pain threshold
and contributes to hypersensitivity to
innocuous stimuli during the post-
operative period, leading to chronic
neuropathic pain. The prevention of
this sensitization can improve the
patient’s postoperative pain and
reduce the risk for the development
of chronic neuropathic pain.13
Preemptive analgesics need to be
relatively easy to administer, provide
rapid onset, and have an adverse-
effect profile that will not
interfere with the planned surgical
procedure. Typically, NSAIDs, such
as cyclooxygenase-2 (COX-2) inhib-
itors, pregabalin, gabapentin, and
acetaminophen, are used for this
purpose and are administered in the
preoperative holding area 1 to 2
hours before incision. These medica-
tions are an important part of multi-
modal anesthesia, and the practice
guidelines for acute pain manage-
February 2016, Vol 24, No 2
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Calin Stefan Moucha, MD, et al
ment in the perioperative setting of scales at 3 and 6 weeks, and Medical
the American Society of Anesthesiol- Outcomes Study 12-Item Short Form
ogists Task Force on Acute Pain (SF-12) disability scores at 6 weeks
Management recommend that a postoperatively.
combination of these medications be
used in the perioperative period, Gabapentinoids
along with neuraxial and regional
Pregabalin and gabapentin work
anesthesia techniques, and supple-
centrally on gamma-aminobutyric
mented with intravenous PCA if
acid (GABA) receptors to reduce
necessary.14
central sensitization at the level of the
spinal cord and brain. Pregabalin is
Cyclooxygenase-2 Inhibitors more potent than gabapentin and
requires a lower dose to achieve the
COX-2 inhibitors work peripherally to
desired effect. It should be noted that
prevent the production of prostaglan-
the perioperative and postoperative
dins. They have a favorable adverse-
administration of these medications
effect profile, with reduced risk for
for acute pain prevention is an off-
gastric ulcers and minimal platelet
label use. A study by Buvanendran
dysfunction compared with traditional
et al18 demonstrated that a one-time
NSAIDs, which are nonspecific COX-
preoperative dose of 150 mg of
1 and COX-2 inhibitors. Although
pregabalin in 9 patients undergoing
COX-2 inhibitors have been impli-
TKA rapidly achieved cerebrospinal
cated in increasing the risk for adverse
fluid concentrations within 2 hours
cardiovascular events, doses of cele-
of administration, equivalent to an
coxib of up to 400 mg a day have not
anticonvulsant level, and peaked by
been shown to increase this risk.15 In a
6 to 8 hours at a concentration high
meta-analysis of eight randomized
enough to prevent allodynia in a rat
controlled trials (RCTs), with a total
model. A randomized double-blind
of 571 patients undergoing TKA who
controlled study of 240 patients
received perioperative COX-2 inhibi-
undergoing TKA compared a pre-
tors, the authors concluded that the
operative dose of 300 mg of pre-
perioperative use of COX-2 inhibitors
gabalin followed by a 14-day taper
resulted in lower pain scores as mea-
with placebo. The study demon-
sured on the visual analog scale (VAS),
strated that the treatment group had
greater range of motion, less opioid
a substantial reduction in chronic
consumption, and a reduction in
neuropathic pain at 6 months post-
opioid-related adverse effects at 3
operatively (0% versus 5.2%). In the
days postoperatively.16 A randomized
acute postoperative period, those who
double-blind placebo-controlled study
received pregabalin required fewer
by Schroer et al17 of 107 patients
epidural opioids and lower amounts of
undergoing TKA suggested clinical
oral opioids, and achieved increased
benefits to the administration of 200
flexion at 30 days.19
mg of celecoxib twice daily for 6
weeks postoperatively. They found
statistically significant reductions in Acetaminophen
total postoperative narcotic pill con- The mechanism of action for aceta-
sumption (76.3 6 55 versus 138 6 minophen is not understood fully,
117; P = 0.003) and VAS pain scores but it is believed to work through
at 3, 6, and 12 weeks in the treatment several centrally mediated pathways,
group. They also noted statistically including as a cannabinoid receptor
significant improvements in knee agonist, as an inhibitor of COX-2
flexion up to 1 year, American Knee isoenzyme, and as an agonist of
Society Scores and Oxford Knee Score transient receptor potential cation
61
Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty
Table 1
Dosage Recommendations for Individual Nonopioid Agents Administered as Part of Multimodal Analgesia
Drug Dose
Ketorolac 15–30 mg
Ibuprofen 800 mg
Celecoxib 400 mg
Gabapentin 300 mg
Pregabalin 75 mg
Propacetamol 2g
Acetaminophen 1g
(Reproduced with permission from Parvizi J, Miller AG, Gandhi K: Multimodal pain management after total joint arthroplasty. J Bone Joint Surg Am
2011;93[11]:1075-1084.)
channel, subfamily V, member 1, a
central antinociceptor.20 Intravenous
acetaminophen can be used for anal-
gesia in all phases of the perioperative
period, is as effective as 10 mg of
intravenous morphine, and avoids
opioid-related adverse effects. It is
also useful in the preoperative period
because it rapidly achieves peak con-
centration in cerebrospinal fluid
within 30 minutes of administration
and is not subject to the delayed
absorption of oral medications.21
General and Neuraxial
Anesthesia
General and/or neuraxial anesthesia
is appropriate for TKA and is familiar
to most surgeons and anesthesiolo-
gists. General anesthesia is associated
with reduced perioperative tissue
oxygen tension22 as well as post-
operative nausea, vomiting, and
delirium, which are avoided by using
neuraxial anesthesia.3 The adminis-
tration of neuraxial anesthesia
requires technical procedural skill,
however, and although usually very
successful, is associated with a fail-
ure rate of approximately 4%,
necessitating conversion to general
anesthesia.23 The complication rate
of spinal and epidural anesthesia has
been reported to be extremely low
(0.03%) but does include serious yet
62
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Route of Administration Time Before Surgery
Oral/intravenous 1–2
Oral 1–2
Oral 1–2
Oral 1–2
Oral 1–2
Oral/intravenous 0–2
Oral/intravenous 0–2
uncommon complications, such as
spinal and epidural hematoma,
abscess formation, cauda equina
syndrome, and meningitis.24 More
common adverse effects include
postoperative hypotension and uri-
nary retention.
A retrospective study by
Memtsoudis et al2 examined
528,495 total joint arthroplasty
patients in a national healthcare
database from 2006 to 2010. The
authors evaluated the types of anes-
thesia used and determined whether
anesthetic choice had any impact
on perioperative outcomes. Com-
paring general anesthesia with neu-
raxial anesthesia in the TKA
subgroup, they found that general
anesthesia was associated with
higher risks of pulmonary compro-
mise (odds ratio [OR], 1.83; 95%
confidence interval [CI], 1.43 to
2.35; P , 0.0001), pneumonia (OR,
1.27; 95% CI, 1.05 to 1.53; P =
0.0083), all infections (OR, 1.38;
95% CI, 1.26 to 1.52; P , 0.0001),
acute renal failure (OR, 1.44; 95%
CI, 1.24 to 1.67; P , 0.0001), and
overall 30-day mortality (OR, 1.83;
95% CI, 1.08 to 3.1; P = 0.0211).
Similarly, a retrospective study by
Pugely et al3 examined the American
College of Surgeons National Sur-
gical Quality Improvement Pro-
gram (ACS NSQIP) database from
2005 to 2010, comparing 30-day
Journal of the American Academy of Orthopaedic Surgeons
Time After Surgery
h 15–30 mg/6 h
h 800 mg/6 h
h 200 mg/12 h (12 h after surgery)
h 300 mg · 1 (24 h after surgery)
h 75 mg · 1 (12 h after surgery)
h 2 g/4 h
h 650 mg/6 h
postoperative complications among
14,052 TKA patients, of whom
6,030 patients (42.9%) received
general anesthesia and of whom
8,022 patients (57.1%) received
neuraxial anesthesia. Patients who
received neuraxial anesthesia had
statistically significant lower rates
of surgical site infection (0.68%
versus 0.92%; P = 0.0003), blood
transfusions (5.02% versus 6.07%;
P = 0.0086), and overall complica-
tions (10.72% versus 12.34%; P =
0.0032) as well as shorter surgical
times (96 versus 100 minutes; P ,
0.0001) and length of stay (3.45
versus 3.77 days; P , 0.0001). The
most noticeable benefits were seen
in patients who had higher Ameri-
can Society of Anesthesiologists
classifications.
The use of epidural anesthesia for
postoperative pain control was
examined in a meta-analysis of eight
RCTs comparing epidural anesthesia
with PNB in 510 patients, 464 of
whom underwent TKA. The meta-
analysis found equivalent pain scores
and morphine consumption between
both groups up to 48 hours post-
operatively. The use of epidural
anesthesia was associated with a
higher incidence of hypotension and
urinary retention, however, suggest-
ing that PNB provides equivalent
pain relief with a more favorable
adverse-effect profile.4

Table 2
Common Peripheral Nerve Block Medications
Medicationa Strength (%)
Lidocaine 1–2
Mepivacaine 1.5–2
Bupivacaine 0.125–0.75
Ropivacaine 0.25–0.75
a
Epinephrine (concentration, 1:200,000 to 1:400,000 [2.5 to 5 mg/mL]) is used to increase maximum dose and duration of a local anesthetic by
delaying systemic absorption via local vasoconstriction.
The American Society of
Regional Anesthesiologists has
published consensus guidelines for
the use of neuraxial anesthesia
and chemothromboprophylaxis. 25
They do not endorse using a twice-
daily or once-daily dosing scheme
of low-molecular-weight heparin
(LMWH) specifically, but they do
note that twice-daily dosing
schemes of LMWH prophylaxis
are associated with a higher risk of
spinal hematoma formation. They
recommend removing an epidural
catheter before any LMWH has
been given and waiting 2 hours
after catheter removal to begin the
initiation of prophylaxis. If
desired, LMWH prophylaxis may
be initiated 6 to 8 hours after
surgery, but 10 to 12 hours must
elapse after the last LMWH
administration before removing
the epidural catheter. In this set-
ting, 2 hours must elapse after
catheter removal before adminis-
tering another dose of LMWH. In
the setting of warfarin use, they
recommend the removal of an
epidural catheter when the inter-
national normalized ratio is ,1.4.
The guidelines mention no specific
concerns with regard to neuraxial
techniques or the timing of cathe-
ter removal in patients treated with
aspirin or NSAIDs.
February 2016, Vol 24, No 2
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Volume Maximum Dose
10–30 mL 4.5 mg/kg, 7 mg/kg with
epinephrine
10–40 mL 4.5 mg/kg, 7.5 mg/kg
with epinephrine
10–40 mL 3 mg/kg with or without
epinephrine
15–30 mL 3 mg/kg with or without
epinephrine
Peripheral Nerve Blocks
PNB often is used in TKA to provide
supplemental anesthesia and analge-
sia during the perioperative and
postoperative periods. The primary
sensory innervation to the knee is
supplied by the femoral nerve ante-
riorly and the posterior cutaneous
nerve of the thigh posteriorly. The
lateral femoral cutaneous nerve
and the obturator nerve provide var-
iable contributions to sensation lat-
erally and medially, respectively. The
degree and pattern of nerve blockade
depends on the targeted nerve and
whether or not the anesthesia is
achieved via a single shot or a con-
tinuous catheter. Some of the pur-
ported benefits of regional anesthesia
include a shorter length of stay;
reduced opioid consumption with a
concomitant reduction in opioid
adverse effects, such as reduced cog-
nition, nausea, vomiting, and pruri-
tus;5,6 a reduced risk of hypotension
and urinary retention compared with
epidural anesthesia;4 and earlier
participation in physical therapy.7
Although regional anesthetic tech-
niques are useful adjuncts in pain
management, they require a special-
ized technical skill on the part of the
anesthesiologist and are associated
with a reported failure rate ranging
Calin Stefan Moucha, MD, et al
Onset Duration
10–20 min 2–5 h anesthesia, up to 8 h
analgesia
10–20 min 2–5 h anesthesia, up to 8 h
analgesia
10–30 min 5–15 h anesthesia, up to
30 h analgesia
10–30 min 4–10 h anesthesia, up to
24 h analgesia
from 0% to 67%.7 The reported
complication rates from regional
anesthesia techniques are low
(0.1%) and include cardiac arrest,
death, seizure, and peripheral nerve
injury.23 Common medications and
dosages used in regional nerve
blocks are listed in Table 2. Femoral
nerve blocks (FNBs) and adductor
canal blocks (ACBs) are among the
most frequently used PNBs in TKA
and, because of recent controversies
in postoperative fall rates,10,11 are
the primary focus in this article.
Three-in-One Perivascular
Femoral Nerve Block
This block targets the femoral nerve in
the femoral canal, relying on diffusion
of the local anesthetic to provide
blockade of the femoral, lateral femo-
ral cutaneous, and obturator nerves.
The term three-in-one FNB is some-
what of a misnomer because the
obturator nerve rarely is anesthetized
successfully using this block. Tradi-
tionally, it has been performed using
nerve stimulation, but ultrasonogra-
phy is now being used increasingly to
reduce the rate of failed blockade and
inadvertent arterial or intraneural
puncture. This block is a mixed motor
and sensory nerve block and results in
numbness of the anterior, lateral, and
medial aspects of the thigh, causing
63
Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty

Table 3
Efficacy of Regional Nerve Blocks
Study (Type) Block No. of Patients Outcomes Measure Result Limitations

Kim et al28 SSACB vs 47 TKA patients in Time points 6–8 h, No difference in Small sample size,
(prospective, SSFNB ACB group 24 h, 48 h morphine underpowered, no
double-blind, 46 TKA patients in Quadriceps strength consumption long-term follow-up
randomized) FNB group tested with and pain scores
dynamometer ACB group had
Morphine better quadriceps
consumption strength at 6–8 h
NRS pain score postop (7.3 kgf
versus 2.2 kgf),
which disappeared
by 24 h
Jæger et al29 CACB vs 25 TKA patients in Quadriceps strength No difference in Small sample size,
(prospective, CFNB ACB group measured with VAS pain scores underpowered, no
double-blind, 29 TKA patients in dynamometer at No difference in long-term follow-up
randomized) FNB group 24 h compared mobility as
with baseline measured by
Mobility with TUG TUG test
test 24 h postop Improved quadriceps
compared with strength in ACB
baseline group compared
VAS pain scores at with FNB group
rest and with at 24 h (52%
motion at 2 h, 4 h, of baseline
8 h, 24 h postop versus 18%)
Morphine
consumption at 2 h,
4 h, 8 h, 24 h postop
Jenstrup et al6 CACB vs 34 TKA patients in Time points 2 h, 4 h, ACB group had Small sample size,
(prospective, placebo ACB group 8 h, 24 h, 26 h lower morphine underpowered, no
double-blind, 37 TKA patients in Total morphine consumption at long-term follow-up
placebo controlled, placebo group consumption 24 h (40 mg
randomized) At 24 h postop, VAS pain scores at versus 56 mg)
the placebo rest and with knee No difference in
group received flexion VAS pain scores
ropivacaine Postop nausea and or postop nausea
vomiting or vomiting
Mobility measured ACB group
by TUG test performed better
on TUG test at
24 h; this difference
disappeared at 26 h
after administration
of ropivacaine in
placebo group

ACB = adductor canal block, CACB = continuous adductor canal block, CFNB = continuous femoral nerve block, FNB = femoral nerve block, kgf =
kilogram force unit, NRS = numeric rating scale, SSACB = single-shot adductor canal block, SSFNB = single-shot femoral nerve block, TKA= total
knee arthroplasty, TUG = timed-up-and-go, VAS = visual analog scale

profound quadriceps weakness. When
this block is performed, the patient is
positioned supine, and ultrasonogra-
phy is used to identify the nerve at the
confluence of the iliacus and psoas
muscles. The needle is inserted from a
laterally based starting point and is
advanced using ultrasonography for
visualization. Ultrasonography is also
used to visualize the injected local
anesthetic layering under and about
the femoral nerve. A catheter may be
inserted for continued analgesia in the
postoperative period.26
The FNB predictably results in
quadriceps weakness, increasing the
risk of fall in the postoperative
period. Some of these falls may be
prevented by mandating that the
patient use a knee immobilizer while
ambulating until able to perform a

64 Journal of the American Academy of Orthopaedic Surgeons

Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.

straight leg raise. Attempts have been
made to vary the concentration of the
anesthetic to reduce the degree of
quadriceps weakness, but the degree
of weakness is fairly consistent
regardless of the concentration or
dosing schedule of the anesthetic
administered.8,9 A recent meta-
analysis by Ilfeld et al10 showed
that the postoperative risk of fall
after receiving an FNB or lumbar
plexus block was 7%. Sharma et al11
examined postoperative falls in their
own institution in patients who
received FNB for TKA over a 2-year
period and found a fall rate of 1.6%,
resulting in a reoperation rate of
0.4%. The benefits of FNB in TKA
patients were examined in a recent
Cochrane Review of 47 RCTs
incorporating 2,710 patients. The
authors found no substantial differ-
ence in pain relief between epidural
anesthesia and FNB for 72 hours
postoperatively (standardized mean
difference [SMD], 20.05; 95% CI,
20.43 to 0.32), but FNB was noted
to produce less nausea and vomiting
(relative risk [RR], 0.63%; 95% CI,
0.41 to 0.97) and greater patient
satisfaction (SMD, 0.6; 95% CI,
0.23 to 0.97).12
Adductor Canal Block
This block is becoming increasingly
popular because it targets several
mostly sensory nerves in the adductor
canal while reducing the degree of
quadriceps weakness. The targeted
nerves include the saphenous nerve,
articular branches of the obturator
nerve, the medial retinacular nerve,
and the nerve to the vastus medialis,
which is the only motor nerve involved
in the blockade. This technique results
in a sensory blockade of the ante-
romedial knee at the level of the
superior pole of the patella and the
medial lower leg, with minimal loss of
quadriceps strength. The block is
performed by positioning the patient
supine, with the ultrasonographic
February 2016, Vol 24, No 2
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
probe applied at the medial mid-distal
thigh level, 2 to 3 cm proximal to the
adductor hiatus. The femoral artery
and vein are located deep to the sar-
torius muscle, with the saphenous
nerve lateral to them at this level. Local
anesthetic is injected around the
saphenous nerve using ultrasonogra-
phy for visualization. A catheter may
be inserted to provide continued anal-
gesia in the postoperative period.27
The ACB has not been examined in
large RCTs, but it has been shown to
be a promising modality in several
smaller studies. Studies comparing
FNBs and ACBs are summarized in
Table 3. Figure 1 demonstrates the
difference between the sensory cov-
erage areas of FNBs and ACBs.
Single-Shot Versus
Continuous Catheter
Infusion Peripheral Nerve
Blocks
Most local anesthetics used in PNBs
wear off within 24 hours of admin-
istration when given as a single shot.
Infusion catheters may be placed at
the time of block administration to
provide continued analgesia in the
postoperative period. A prospective
nonblinded randomized study com-
pared postoperatively placed contin-
uous FNBs with single-shot FNBs in
36 TKA patients, with catheter
removal on postoperative day 2 for the
continuous group. The authors found
that patients who had the continuous
catheter infusion FNB had lower VAS
scores at rest and during activity than
did the patients who received the single-
shot FNB, beginning on postoperative
day 1 and continuing until post-
operative day 3. The continuous cath-
eter infusion FNB group also consumed
less total morphine during the hospital
stay. No differences were seen in length
of stay or knee flexion at 6 and 12
weeks postoperatively.30 These find-
ings agree with those of the Cochrane
Review of FNBs, which found
moderate-quality to high-quality evi-
Calin Stefan Moucha, MD, et al
Figure 1
Clinical photograph of the lower
extremities demonstrating the
difference in sensory coverage
between a femoral nerve block
(FNB) and an adductor canal block
(ACB). The sensory component of
the three-in-one FNB affects the
lateral femoral cutaneous nerve, the
obturator nerve, and the sensory
branches of the femoral nerve, which
are the anterior femoral cutaneous
nerve and the saphenous nerve. The
sensory component of the ACB
affects the saphenous nerve and
anesthetizes the anteromedial
aspect of the leg from the superior
pole of the patella proximally to the
anteromedial ankle distally. The
degree of proximal coverage is
operator dependent. Large-volume
injections of 30 to 40 mL may spread
proximally along the adductor canal
and cause an undesired sensory and
motor blockade similar to that of FNB.
dence that continuous catheter infusion
FNBs improve pain scores both at rest
(SMD, 0.62; 95% CI, 21.17 to
20.07) and with movement (SMD,
20.42; 95% CI, 20.67 to 20.17) and
reduce morphine consumption (mean
difference, 213.81 mg; 95% CI,
223.27 to 24.35) compared with
single-shot blocks.12
Alternative Peripheral Nerve
Blocks
Several other PNBs are available,
such as the psoas compartment
65
Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty
Table 4
Common Periarticular Injection Medications
Medication Dose
Corticosteroid 40 mg methylprednisolone Anti-inflammatory effects via inhibition
124 mg betamethasone
Clonidine 80 mg
Ketorolac 15230 mg
Morphine 4210 mg
Amide 202400 mg bupivacaine Long-acting anesthetic:
anesthetic 1502400 mg ropivacaine
Epinephrine 3002600 mg
1:1000
Antibiotics 750 mg cefuroxime
Vancomycin if patient has
penicillin allergy
AV = atrioventricular, LIA = local infiltration anesthesia
lumbar plexus block, the fascia
iliaca block, and the sciatic nerve
block (SNB), which also can provide
suitable anesthesia and analgesia in
TKA.26 Perhaps the most useful
alternative PNB is the SNB because
it provides anesthesia to the pos-
terior aspect of the knee. When
combined with an FNB, it theoret-
ically provides more complete
postoperative pain relief. The use of
SNB should be restricted to patients
with varus deformity of the knee
because it may complicate the
interpretation of a postoperative
neurovascular examination in
patients with valgus deformity. A
systematic review by Abdallah and
Brull31 included four RCTs and
three observational studies com-
paring SNB plus FNB with SNB
alone in 391 TKA patients and
suggested that modest improve-
ments in VAS pain scores and opi-
oid consumption occur within the
first 24 hours postoperatively when
using a combination of SNB plus
66
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Desired Effect
of prostaglandins and leukotrienes
a-2 adrenergic receptor agonist
producing synergistic effects with
local anesthetics and opioids
NSAID preventing prostaglandin
production
Local, regional, and central opioid
receptor agonist
bupivacaine t1/2 3.5 h
ropivacaine t1/2 4.2 h
Nonselective adrenergic receptor
agonist causing vasoconstriction,
delaying systemic absorption of the
LIA drug mixture
Prevention of surgical site infection
FNB. The heterogeneity of the
studies made it impossible to per-
form a meta-analysis, however.
Local Infiltration Analgesia
Interest in local infiltration anesthesia
(LIA) has been increasing since Busch
et al32 performed the first high-quality
prospective RCT to compare the
efficacy of LIA plus PCA and PCA
alone administered for postoperative
pain control after TKA with regard to
postoperative pain scores, morphine
consumption, and patient satisfac-
tion. They found a statistically sig-
nificant reduction (P , 0.001) in
morphine consumption within the
first 24 hours postoperatively in the
group that received LIA, along with
statistically significant improvement
in VAS pain scores (P = 0.007) and
VAS patient satisfaction scores (P =
0.013) at 4 hours postoperatively.
LIA consists of an intraoperative
injection of a compound mixture of
Journal of the American Academy of Orthopaedic Surgeons
Potential Adverse Effects
Hyperglycemia, increased risk of
infection
Hypotension, bradycardia, pruritus,
AV block, sedation
Platelet dysfunction, renal toxicity
Nausea, pruritus, confusion,
respiratory depression
Cardiotoxicity, hepatotoxicity,
hypotension, nausea, vomiting,
bradycardia, tinnitus
Hypertension, tachycardia,
arrhythmias, pulmonary edema
Renal toxicity
medications, most often including a
long-acting anesthetic, an NSAID,
and epinephrine, which is adminis-
tered to the posterior capsule, collat-
eral ligaments, capsular incision,
quadriceps tendon, and sub-
cutaneous tissues. Wide variability
exists in the strength of the medica-
tion and in the type of medications
combined in LIA cocktails. Some LIA
cocktails also may include cortico-
steroids instead of NSAIDs, antibi-
otics, and clonidine. Common LIA
medications are listed in Table 4 and
common LIA cocktails are listed in
Table 5.
To understand the essential com-
ponents of a LIA cocktail, Kelley
et al33 evaluated the postoperative
pain relief provided by four different
periarticular injection admixtures in
150 patients undergoing TKA. They
found that patients who had received
periarticular injections containing
ropivacaine, ketorolac, and epi-
nephrine with or without clonidine,
had substantially less pain in the
 Calin Stefan Moucha, MD, et al

Table 5
Common Local Infiltration Anesthesia Cocktails
Study Components Administration

Busch et al32 400 mg ropivacaine (80 mL of 0.5%
ropivacaine at 5 mg/mL)
30 mg ketorolac (1 mL at 30 mg/mL)
0.6 mg of 1:1000 epinephrine (0.6 mL
at 1 mg/mL)
5 mg epimorphine (0.5 mL at 10 mg/mL)
Kelley et al33 246.25 mg ropivacaine (49.25 mL
of 0.5% ropivacaine at 5 mg/mL)
0.5 mg 1:1000 epinephrine (0.5 mL
at 1 mg/mL)
30 mg ketorolac (1 mL at 30 mg/mL)
0.08 mg clonidine (0.8 mL at 1 mg/10 mL)
Parvataneni et al34 2002400 mg bupivacaine (40 mL of 0.5%
bupivacaine [200 mg] at 5 mg/mL or 53 mL
of 0.75% bupivacaine [400 mg] at 7.5 mg/mL)
4210 mg morphine sulfate (0.421 mL
at 10 mg/mL)
0.3 mg of 1:1000 epinephrine (0.3 mL
at 1 mg/mL)
40 mg methylprednisolone acetate (1 mL
at 40 mg/mL) (contraindicated in diabetic
or immune-compromised patients)
750 mg cefuroxime (substitute vancomycin
if patient has penicillin allergy)
Dilute cocktail to a total volume of 100 mL using
normal saline. Prior to component implantation,
inject 20 mL into posterior capsule and medial
and lateral collateral ligaments. During cement
curing, inject 20 mL into quadriceps and
retinacular tissues. After component
implantation, inject 60 mL into fat and
subcuticular tissues.
Dilute cocktail to a total volume of 100 mL using
normal saline. Prior to component implantation,
inject 9 mL into posterolateral soft tissues and
lateral femoral periosteum, 10 mL into
posteromedial soft tissues and medial femoral
periosteum, and 1 mL into PCL. After component
implantation, inject 25 mL into medial meniscus
remnant and inferomedial capsule, 25 mL into
superomedial capsule, 10 mL into lateral
capsule, 10 mL into medial subcutaneous
tissues, and 10 mL into lateral subcutaneous
tissues.
Dilute cocktail to a total volume of 60 mL using
normal saline. After components cemented, but
before liner is inserted, inject 15 mL into posterior
capsule and posteromedial and posterolateral
structures. After liner is inserted and knee is
reduced, inject remaining 45 mL into extensor
mechanism, synovium, capsule, pes anserinus,
anteromedial capsule, periosteum, iliotibial
band, and collateral ligaments and origins.
Before final dressing, apply transdermal
clonidine patch (100 mg/24 h).

PCL = posterior cruciate ligament

immediate postoperative period than
did those patients who received
injections containing ropivacaine
and epinephrine alone, suggesting
that ketorolac is a key component of
the injection. Parvataneni et al34
performed an RCT of 60 TKA
patients assigned to receive LIA or
FNB plus PCA postoperatively. Both
groups also received a standardized
multimodal oral analgesic protocol.
The authors found that the LIA
group had an improved ability to
perform a straight leg raise on
postoperative day 1 (63% [31
patients] versus 21% [29 patients]; P
, 0.05), with similar pain scores
between both groups during their
postoperative hospital course, sug-
gesting that LIA provides pain con-
trol equivalent to that of FNB while
maintaining quadriceps motor
strength.
Similar findings were also demon-
strated by Spangehl et al35 in a non-
blinded RCT of 160 patients
undergoing primary TKA who were
randomized to receive either a con-
tinuous femoral nerve catheter and
single-shot SNB (79 patients) or an
LIA cocktail of ropivacaine, ketoro-
lac, epinephrine, and morphine (81
patients). The authors noted no dif-
ference in postoperative pain scores
between the two groups during
the first two postoperative days.
Although the LIA group had a
shorter average length of stay com-
pared with the PNB group (2.44 and
2.84 days, respectively), on average,
the LIA group consumed more
morphine on the first day after sur-
gery. Notably, the patients in the
PNB group, compared with the LIA
group, experienced more acute
postoperative falls (3 and 0, respec-
tively), lower quadriceps function as
measured by the ability to perform a
straight leg raise on postoperative day
1 (24% and 79%, respectively), and
more peripheral nerve dysesthesias
(12% and 1.3%, respectively) at 6
weeks postoperatively. Studies com-
paring the effectiveness of LIA with

February 2016, Vol 24, No 2 67

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Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty

Table 6
Efficacy of Local Infiltration Anesthesia
Outcome
Study (Type) Comparison No. of Patients Measures Results Limitation

Busch et al32 LIA 1 PCA vs 66 TKA patients in

Morphine LIA group No power analysis,
(prospective, PCA only LIA group consumption at consumed less no mobility testing,
single-blind, 70 TKA patients in6 h, 12 h, 18 h, 24 h morphine at 6 h no mention of
randomized PCA-only group total and 12 h and total opioid-related
controlled trial) VAS pain scores at morphine at 24 h adverse effects
4 h, 1 d, 3 d, 5 d, VAS scores were
2 wk lower only in LIA
ROM at 6 wk group at 4 h
LOS No difference in LOS
No difference in
ROM at 6 wk
Parvataneni et al34 LIA vs 31 TKA patients in VAS pain scores No difference in Underpowered,
(prospective, FNB 1 PCA LIA group each POD, 6 wk, VAS scores on missing datasets
nonblinded, 29 TKA patients in and 3 mo POD 1 (daily VAS scores,
randomized FNB 1 PCA group Total opioid No difference in daily patient
controlled trial) consumption patient satisfaction
Patient satisfaction satisfaction on scores, total
SLR POD 1 and POD 1 morphine
knee ROM POD 2 LIA group better able consumption),
LOS to perform SLR nonvalidated
POD 1 (63% vs patient
21%) satisfaction
No difference in LOS measurement tool
Spangehl et al35 LIA vs 81 TKA patients in VAS pain scores PNB group with Nonblinded, VAS
(prospective, CFNB 1 SNB LIA group each POD to lower VAS score pain score
nonblinded 79 TKA patients in POD 2 on DOS, but no evaluated at rest
randomized CFNB 1 SNB Morphine difference only, study only
controlled trial) group consumption thereafter adequately
SLR POD 1 and 2 LIA group had powered to
LOS higher narcotic evaluate primary
Neurologic changes consumption on outcome (VAS
at 6 wk DOS, but pain score)
equivalent
thereafter
LIA group better
able to perform
SLR POD 1 (79%
vs 24%)
LIA group had
shorter LOS (2.44
vs 2.84 d)
PNB group had
more persistent
dysesthesias
at 6 wk than
LIA group (9
patients vs
1 patient)
(continued )
CFNB = continuous femoral nerve block, DOS = day of surgery, FNB = femoral nerve block, LIA = local infiltration anesthesia, LOS = length of stay,
PCA = patient-controlled analgesia, PNB = peripheral nerve block, POD = postoperative day, ROM = range of motion, SLR = straight leg raise, SNB =
sciatic nerve block, TKA = total knee arthroplasty, VAS = visual analog scale

other pain-management modalities approved for use in the United States. controlled release, thus minimizing
are summarized in Table 6. This formulation is purported to the risk of bupivacaine toxicity. It is
Recently, a delayed-release liposo- provide long-acting pain relief of up surgeon administered in the same
mal formulation of bupivacaine was to 72 hours postoperatively via a manner as a traditional periarticular

68 Journal of the American Academy of Orthopaedic Surgeons

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 Calin Stefan Moucha, MD, et al

Table 6 (continued )
Efficacy of Local Infiltration Anesthesia
Outcome
Study (Type) Comparison No. of Patients Measures Results Limitation

Jiang et al36 LIA vs placebo 21 RCTs, 10 of VAS scores 0248 h Lower VAS score in Studies had small
(meta-analysis of which involve Morphine LIA group at 6 h, sample sizes, no
level I and II TKA, with total of consumption 24 h, 48 h American studies
randomized 1,280 patients 0248 h Less opioid included, low to
controlled trials) Knee ROM consumption at moderate quality
LOS 24 h and 48 h in of evidence
Opioid adverse LIA group
effects Greater knee ROM
Infection and in LIA group at
wound 24 h, 48 h, 72 h
complication rate No difference in
LOS
Fewer opioid-
related adverse
effects in LIA
group
No difference in
wound
complication or
infection rate

CFNB = continuous femoral nerve block, DOS = day of surgery, FNB = femoral nerve block, LIA = local infiltration anesthesia, LOS = length of stay,
PCA = patient-controlled analgesia, PNB = peripheral nerve block, POD = postoperative day, ROM = range of motion, SLR = straight leg raise, SNB =
sciatic nerve block, TKA = total knee arthroplasty, VAS = visual analog scale

local infiltration injection using mul-
tiple passes with a 25-gauge needle to
inject small aliquots. Importantly, it
must be administered in isolation
because admixture with non-
bupivacaine- or nonliposomal-based
anesthetics may cause an inadvertent
immediate release of the bupivacaine.
The concomitant administration of
nonliposomal bupivacaine with
liposomal bupivacaine is not recom-
mended and should be done with
caution because this can alter the
pharmacokinetics of the liposomal
bupivacaine, resulting in local anes-
thetic toxicity. When considering LIA
strategies, it is important to note that
the average wholesale price of a single
20-mL vial containing 266 mg of
liposomal bupivacaine is 95 times
more expensive than a 10-mL vial of
traditional 0.25% bupivacaine ($285
and $3, respectively).37
In an industry-sponsored pro-
spective RCT on postoperative pain
relief using LIA in TKA patients,
Bramlett et al38 examined varying
doses of liposomal bupivacaine
(133 to 532 mg) compared with a
control of nonliposomal bupivacaine
(150 mg). The liposomal bupivacaine
group had substantially reduced pain
scores compared with control subjects
at a dose that was twice the recom-
mended value (532 mg), and this
benefit was seen only on postoperative
day 1. Bagsby et al39 reported similar
results in a retrospective cohort study
of 150 consecutive TKA patients,
comparing liposomal bupivacaine
with a traditional periarticular injec-
tion of ropivacaine, morphine, and
epinephrine. They did not find any
difference between the two groups in
the amount of pain experienced in the
first 24 hours after surgery or in
morphine consumption during the
entire hospital stay. After the first
postoperative day, the traditional LIA
group actually experienced less self-
reported pain during the remaining
hospital stay compared with the
liposomal bupivacaine group (4.4
versus 4.9 on the VAS pain scale). In a
prospective single-blind RCT per-
formed by Collis et al,40 105 con-
secutive patients undergoing primary
TKA with a single surgeon were
randomized to receive LIA with either
liposomal bupivacaine (54 patients)
or a standard LIA cocktail of ropi-
vacaine, ketorolac, epinephrine, and
clonidine (51 patients). The authors
found no statistical differences in
morphine consumption, pain scores,
knee range of motion, length of stay,
or walking distances at any time point
out to 8 weeks postoperatively.
Schroer et al41 reported similar results
in a prospective single-blind RCT of
111 consecutive patients undergoing
primary TKA with a single surgeon.
The patients were randomized to
receive either liposomal bupivacaine
mixed with nonliposomal bupiva-
caine (58 patients) or nonliposomal
bupivacaine alone (53 patients). The
authors also reported no statistical

February 2016, Vol 24, No 2 69

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Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty

Table 7
Comparison of Liposomal Bupivacaine With Nonliposomal Bupivacaine LIA Cocktails
Outcome
Study (Type) Comparison No. of Patients Measures Results Limitation

Bramlett et al38 LB vs NLB 144 TKA patients NRS pain scores at Only the 532-mg Industry-
(industry- randomized to 1 d, 2 d, 3 d, 4 d, 5 d LB group had sponsored,
sponsored, receive 133 mg AUC of total NRS difference in NRS underpowered,
multicenter, LB, 266 mg LB, pain scores pain score and 532 mg of LB is
double-blind, 399 mg LB, Patient satisfaction only on POD 1 twice maximum
randomized 532 mg LB, or on POD 8 compared with recommended
controlled trial) 150 mg NLB NLB, which is dose of 266 mg,
twice the no evaluation of
maximum dose mobility or knee
recommended ROM,
for single nonvalidated
administration patient
No difference in satisfaction
AUC of NRS pain measurement
scores between tool, no long-term
groups follow-up
Patient satisfaction
higher only in the
532-mg LB group
Bagsby et al39 LIA (ropivacaine, 85 TKA patients Average VAS pain No difference in Retrospective, no
(retrospective epinephrine, in LIA group scores for 24 h VAS pain score at evaluation of
case-control) morphine) vs LB 65 TKA patients and until 24 h, LIA group mobility or knee
in LB group discharge had lower VAS ROM, no long-
Total morphine pain score for term follow-up
consumption remainder of
hospital stay
No difference in
total morphine
consumption
Collis et al40 LIA (ropivacaine, 51 TKA patients VAS pain scores No difference in No power analysis,
(prospective, ketorolac, in LIA group at rest and with VAS scores at missing P values,
single-blind, epinephrine, 54 TKA patients activity on POD 1, rest or with no mention of
randomized clonidine) vs LB in LB group 2, 3, 2 wk, 428 wk activity at any adverse events,
controlled trial) Morphine time point no assessment of
consumption between the two baseline narcotic
POD 1, 2, 3, groups usage or VAS
2 wk, 428 wk No difference in pain scores
Active knee ROM narcotic
POD 1, 2, 3, 2 wk, consumption
428 wk at any time point
Walking distance between the two
(ft) POD 1, 2, 3 groups
No difference in
knee ROM
No difference in
ambulation
distance
(continued )
AUC = area under the curve, LB = liposomal bupivacaine, LIA = local infiltration anesthesia, NLB = nonliposomal bupivacaine, NRS = numerical
rating scale, POD = postoperative day, ROM = range of motion, TKA = total knee arthroplasty, VAS = visual analog scale

differences in morphine consump-
tion, pain scores, length of stay, or
knee range of motion out to 3 weeks
postoperatively. Current available
evidence suggests no added benefit to
using liposomal bupivacaine instead of
a traditional LIA cocktail in primary
TKA. Larger RCTs are needed to
clarify whether any cost-benefit of
liposomal bupivacaine exists com-
pared with traditional LIA cocktails in
TKA. Studies comparing the effec-
tiveness of liposomal bupivacaine with
traditional periarticular injections are
summarized in Table 7.

70 Journal of the American Academy of Orthopaedic Surgeons

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Table 7 (continued )
Comparison of Liposomal Bupivacaine With Nonliposomal Bupivacaine LIA Cocktails
Study (Type) Comparison
Schroer et al41 LB 1 NLB vs NLB 58 TKA patients
(prospective,
single-blind,
randomized
controlled trial)
AUC = area under the curve, LB = liposomal bupivacaine, LIA = local infiltration anesthesia, NLB = nonliposomal bupivacaine, NRS = numerical
rating scale, POD = postoperative day, ROM = range of motion, TKA = total knee arthroplasty, VAS = visual analog scale
Effect of Multimodal
Anesthesia on Length of
Stay
Assessing whether multimodal tech-
niques can reduce the length of
hospital stay after TKA can be chal-
lenging because a variety of factors,
such as patient preconceptions,
medical comorbidities, postoperative
complications, and social factors, can
play a role in determining the overall
length of stay. A retrospective study
by Peters et al42 examining the
application of a multimodal anes-
thesia protocol to 200 total joint
arthroplasty patients (100 TKAs)
highlighted this difficulty. In the
TKA subgroup, the average length of
stay was 3.1 days in the traditional
group versus 3 days in the multi-
modal group (P = 0.7). Of the 50
TKA patients who received multi-
modal anesthesia, however, 2 had
postoperative complications, ren-
dering them outliers in the statistical
analysis of the effect of multimodal
anesthesia on length of stay.
Removal of these patients from the
analysis reduced the average length
of stay in the multimodal group to
February 2016, Vol 24, No 2
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Outcome
No. of Patients Measures
VAS pain score at No difference in Power analysis
in LB group POD 1, 2, 3 AM
53 TKA patients and PM
in NLB group Mean total No difference in
morphine
consumption
during hospital
stay No difference in
Postoperative
nausea
Knee ROM on
POD 2 and 3 wk No difference in
2.5 days (P = 0.002). In a more
recent prospective randomized con-
trolled study by Lamplot et al,43 36
TKA patients were randomized to
receive a periarticular injection and
multimodal oral analgesics or PCA.
The authors reported no difference
in length of stay between the multi-
modal group and the PCA group
(1.9 days and 2.3 days, respectively).
Summary
Postoperative pain control following
TKA and related medication adverse
effects remains a driver of patient
satisfaction and postoperative com-
plications and may present a barrier
to patient discharge. Furthermore, a
mounting body of evidence suggests
that the choice of perioperative
anesthesia in TKA may influence the
risk of postoperative complications
and the mortality rate. A combina-
tion of multimodal analgesia, pre-
emptive analgesia, and neuraxial
anesthesia is supplemented by either
a PNB, periarticular injection, or
both to effectively control post-
operative pain while minimizing
opioid-related adverse effects and
Calin Stefan Moucha, MD, et al
Results Limitation
VAS score at done post-hoc,
any time point VAS pain scores
at rest only, no
mean total mention of
morphine adverse
consumption outcomes, no
assessment of
incidence of quadriceps
postoperative strength or ability
nausea to ambulate
knee ROM on
POD 2 or at 3 wk
improving patient satisfaction. The
ability of multimodal analgesic proto-
cols to reduce the length of hospital
stay, although promising, is still con-
troversial, and further investigation
with large high-quality RCTs is war-
ranted. The surgeon should collaborate
with anesthesia and pain-management
colleagues to develop a multimodal
protocol that suits the skills of all the
physicians involved in the care of the
patient undergoing TKA.
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