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JointEvidence 13/2009 Lit. No. 1794-e
The multimodal pain management approach in total knee arthroplasty
Table of contents
I Introduction 3II Multimodal approach to pain management 3III Purpose 4IV Literature search 4V Results 4VI Conclusions 4VII References 5
K_JE_PainManagement_TKA_08.indd 1 26.3.2009 17:49:50 Uhr
AuThorsMohit Bhandari, MD, MSc, FRCSC–Canada Research Chair, Department of Surgery, McMaster University, Hamilton, OntarioGeorge Mathew, MBBS, MSc, FRCS –Research Fellow, Orthopaedic Research Fellow, McMaster University, Canadasheila sprague, MSc–Clinical Research Project Manager, Senior Research Coordinator, Clarity-Orthopaedic Research, McMaster UniversityCheryl Wylie, BSc (cand.)–Research Assistant, Clarity–Orthopaedic Research, McMaster University
rEviEWEd ByMark A snyder, Md, The Robert S. Heidt, Sr., Wellington Foundation, 2123 Auburn Ave., Suite 624, Cincinnati, Ohio
Published March 2009, Copyright © 2009 byKLEOS, Erlenstrasse 4a, 6343 Rotkreuz, SwitzerlandPhone +41 41 798 41 11, Fax +41 41 798 41 [email protected]. No. 1794-e Ed. 13/09
LisT oF TABLEs
Table 1: Summary of key randomized controlled trials on the multimodal approach to pain management 7
LisT oF ABBrEviATioNs
AUC Area Under CurveDVT Deep Venous Thrombosish Hourmg Milligramsmicrog See mugmin Minutesml Millilitersmug Microgramn NumberP ProbabilityPCA Patient-controlled analgesiaPO OralROM Range of MotionSD Standard DeviationTKA Total Knee ArthroplastyTKR Total Knee ReplacementVAS Visual Analog Scale
Disclaimer Great care has been taken to maintain the accuracy of the information contained in the publication. However, neither KLEOS, nor the authors can be held responsible for errors or any consequences arising from the use of the information contained in this publication. The statements or opinions contained in editorials and articles in this journal are solely those of the authors thereof and not of KLEOS. The products, procedures, and therapies described are only to be applied by certified and trained medical professionals in environments specially designed for such procedures. No suggested test or procedure should be carried out unless, in the reader’s professional judgment, its risk is justified. Because of rapid advances in the medical sciences, we recommend that independent verification of diagnosis, drugs dosages, and operating methods should be made before any action is taken. Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer. Some of the products, names, instruments, treatments, logos, designs, etc. referred to in this journal are also protected by patents and trademarks or by other intellectual property protection laws even though specific reference to this fact is not always made in the text. Therefore, the appearance of a name, instrument, etc. without designation as proprietary is not to be construed as a representation by the publisher that it is in the public domain. This publication, including all parts thereof, is legally protected by copyright. Any use, exploitation or commercialization outside the narrow limits of copyrights legislation, without the publisher’s consent, is illegal and liable to prosecution. This applies in particular to photostat reproduction, copying, scanning or duplication of any kind, translating, preparation of microfilms and electronic data processing and storage. Institutions’ subscriptions allow to reproduce tables of content or prepare lists of articles including abstracts for internal circulation within the institutions concerned. Permission of the publisher is required for resale or distribution outside the institutions. Permission of the publisher is required for all other derivative works, including compilations and translations. Permission of the publisher is required to store or use electronically any material contained in this journal, including any article or part of an article. For inquiries contact the publisher at the address indicated.
13/2009 pAGE – 2JointEvidence
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i introductionTotal knee replacement (TKR) is a safe and cost-effective treatment for alleviating pain
and restoring physical function in patients who do not respond to nonsurgical therapies. Postoperative pain is commonly reported following total knee arthroplasty. It is often acute and obvious in etiology and must be managed to the best ability of the treating surgeon. However, postoperative pain management is not always straightforward and can often be poorly managed. In addition, strategies to reduce postoperative nausea and vomiting are necessary to complement the pain management program. Consequences of uncontrolled pain following total knee arthroplasty include the inability to actively participate in therapy, a delayed recovery, poor or suboptimal surgical outcomes, prolonged hospitalization, and an increased use of health care resources. Pain management using a standardized preoperative, perioperative, and postoperative protocol enhances patients’ ability to undergo successful rehabilitation.
ii Multimodal approach to pain managementThe recent literature suggests that orthopedic surgeons must change the way they have
traditionally thought about postoperative pain management following total knee arthroplasty. Orthopedic surgeons need to consider perioperative pain management as well as strategies to reduce postoperative nausea and vomiting to complement the pain management program. This effort involves more than just increasing the dose of pain medication [1].
Multimodal analgesia is a multidisciplinary approach to pain management with the goal of maximizing the analgesic effect and minimizing the side effects of the medications [2]. Preemptive analgesia is the foundation of the multimodal program because many of the negative effects of analgesic therapy are related to postoperatively administered parenteral opioids, limiting their use is a major principle of multimodal analgesia [1].
A multimodal approach may typically include administering preoperative antiinflammatories starting 48 hours in advance of surgery, an aggressive perioperative antiemetic program, blood loss management, regional nerve catheters for total knee replacement, scheduled narcotics with additional pain medications, and less-invasive surgical techniques [1]. The goal of the multimodal therapeutic approach is to preempt the pain signals, prevent postoperative nausea and vomiting, and attack these problems using different modalities [1].
The multimodal program is one that provides pain prevention at all three levels of pain control: the local wound receptors, the spinal cord, and the brain [2]. The multimodal approach targets different areas of the pain pathway. For example, celecoxib inhibits prostaglandin synthesis, primarily via the inhibition of cyclooxygenase-2 enzyme, reducing the inflammatory mediated pain signals [1]. The mechanism of hydrocodone or oxycodone is not precisely understood, but it is believed to work on opiate receptors in the central nervous system to inhibit pain [1]. Acetaminophen elevates the pain threshold, effectively improving analgesia [1]. Medications should also be prescribed to prevent postoperative nausea and vomiting, such as around-the-clock, scheduled, antiemetics [1].
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iii purposeThe purpose of this review is to provide a summary of the high-quality literature on the
multimodal approach to pain management in patients undergoing total knee arthroplasty or total hip arthroplasty.
iv Literature searchA systematic search of the Cochrane Library and PubMed was conducted to identify
meta-analyses and randomized controlled trials on multimodal pain management. Keywords included multimodal approach, pain management, total joint replacement, total joint arthroplasty, total knee replacement, and total knee arthroplasty. Limits were set to English, randomized controlled trials, and meta-analyses.
v resultsThe systematic search did not identify any relevant meta-analyses on the multimodal
approach to pain management. Multiple searches of PubMed identified 27 key randomized controlled trials which are summarized in Table 1 [3–29]. The randomized controlled trials used various combinations of medications in their multimodal pathways, some of which improved patient outcomes, while others did not. Many of the trials were limited by small sample sizes, so it is difficult to make conclusive recommendations based upon their results.
vi ConclusionsA multimodal pain management program should limit the use of parenteral narcotics and
avoid the side effects of nausea and vomiting, which is one of the most important factors for in-hospital satisfaction [2]. A number of different multimodal approaches to pain management in patients undergoing total knee arthroplasty exist. Implementing a multimodal approach to pain management is something that all total joint surgeons, from high volume to occasional, can do to make a positive impact on patient care and hopefully improve patient outcomes. The optimal combination of medications to include in the multimodal approach remains unknown despite several randomized controlled trials evaluating different components. Future research is required to determine the optimal multimodal approach in managing pain following total knee arthroplasty.
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vii references1. Monesmith, EA (2006). Managing pain after total joint arthroplasty. Orthopaedic Technology Review; 8(1): http://www.orthopedictechreview.com/issues/jan06/pg26.htm, accessed November 2007.
2. dorr, Ld, Chao, L (2007). The emotional state of the patient after total hip and knee arthroplasty. Clin Orthop Relat Res; 463:7–12.
3. Kardash, K, hickey, d, Tessler, MJ, et al (2007). Obturator versus femoral nerve block for analgesia after total knee arthroplasty. Anesth Analg; 105:853–858.
4. Andersen, LJ, poulsen, T, Krogh, B, et al (2007). Postoperative analgesia in total hip arthroplasty: a randomized double-blinded, placebo-controlled study on peroperative and postoperative ropivacaine, ketorolac, and adrenaline wound infiltration. Acta Orthop; 78:187–92.
5. Busch, CA, shore, BJ, Bhandari, r, et al (2006). Efficacy of periarticular multimodal drug injection in total knee arthroplasty. A randomized trial. J Bone Joint Surg Am; 88:959–63.
6. vendittoli, pA, Makinen, p, drolet, p, et al (2006). A multimodal analgesia protocol for total knee arthroplasty. A randomized, controlled study. J Bone Joint Surg Am; 88:282–289.
7. Barrington, MJ, olive, d, Low, K, et al (2005). Continuous femoral nerve blockade or epidural analgesia after total knee replacement: a prospective randomized controlled trial. Anesth Analg; 101:1824–1829.
8. Buvanendran, A, Kroin, Js, Tuman, KJ, et al (2003). Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial. JAMA; 290:2411–2418.
9. Camu, F, Beecher, T, recker, dp, et al (2002). Valdecoxib, a COX-2-specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty. Am J Ther; 9:43–51.
10. Adam, F, Chauvin, M, du Manoir, B, et al (2005). Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty. Anesth Analg; 100:475–480.
11. stiller, Co, Lundblad, h, Weidenhielm, L, et al (2007). The addition of tramadol to morphine via patient-controlled analgesia does not lead to better post-operative pain relief after total knee arthroplasty. Acta Anaesthesiol Scand; 51:322–330.
12. parvataneni, hK, shah, vp, howard, h, et al (2007). Controlling pain after total hip and knee arthroplasty using a multimodal protocol with local periarticular injections: a prospective randomized study. J Arthroplasty; 22(6 Suppl 2):33–8.
13. Long, WT, Ward, sr, dorr, Ld, et al (2006). Postoperative pain management following total knee arthroplasty: a randomized comparison of continuous epidural versus femoral nerve infusion. J Knee Surg; 19:137–143.
14. Kim, MK, Nam, sB, Cho, MJ, et al (2007). Epidural naloxone reduces postoperative nausea and vomiting in patients receiving epidural sufentanil for postoperative analgesia. Br J Anaesth; 99:270–275.
15. han, Cd, Lee, dh, yang, ih (2007). Intra-synovial ropivacaine and morphine for pain relief after total knee arthroplasty: a prospective, randomized, double blind study. Yonsei Med J; 48:295–300.
16. Toftdahl, K, Nikolajsen, L, haraldsted, v, et al (2007). Comparison of peri- and intraarticular analgesia with femoral nerve block after total knee arthroplasty: a randomized clinical trial. Acta Orthop; 78:172–179.
17. inan, N, ozcan, N, Takmaz, sA, et al (2007). Efficacy of lornoxicam in postoperative analgesia after total knee replacement surgery. Agri; 19:38–45.
18. Chu, Cp, yap, JC, Chen, pp, et al (2006). Postoperative outcome in Chinese patients having primary total knee arthroplasty under general anaesthesia/intravenous patient-controlled analgesia compared to spinal-epidural anaesthesia/analgesia. Hong Kong Med J; 12:442–447.
19. Zaric, d, Boysen, K, Christiansen, et al (2006). A comparison of epidural analgesia with combined continuous femoral-sciatic nerve blocks after total knee replacement. Anesth Analg; 102:1240–1246.
20. seet, E, Leong, WL, yeo, As, et al (2006). Effectiveness of 3-in-1 continuous femoral block of differing concentrations compared to patient controlled intravenous morphine for post total knee arthroplasty analgesia and knee rehabilitation. Anaesth Intensive Care; 34:25–30.
21. Casey, G, Nortcliffe, sA, sharpe, p, et al (2006). Perioperative nimodipine and postoperative analgesia. Anesth Analg; 102:504–508.
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22. Axelsson, K, Johanzon, E, Essving, p, et al (2005). Postoperative extradural analgesia with morphine and ropivacaine. A double-blind comparison between placebo and ropivacaine 10 mg/h or 16 mg/h. Acta Anaesthesiol Scand; 49:1191–1199.
23. yadeau, JT, Cahill, JB, Zawadsky, MW, et al (2005). The effects of femoral nerve blockade in conjunction with epidural analgesia after total knee arthroplasty. Anesth Analg; 101:891–895.
24. Nechleba, J, rogers, v, Cortina, G, et al (2005). Continuous intra-articular infusion of bupivacaine for postoperative pain following total knee arthroplasty. J Knee Surg; 18:197–202.
25. Farag, E, dilger, J, Brooks, p, et al (2005). Epidural analgesia improves early rehabilitation after total knee replacement. J Clin Anesth; 17:281–285.
26. pham dang, C, Gautheron, E, Guilley, J, et al (2005). The value of adding sciatic block to continuous femoral block for analgesia after total knee replacement. Reg Anesth Pain Med; 30:128–133.
27. Förster, JG, rosenberg, ph (2004). Small dose of clonidine mixed with low-dose ropivacaine and fentanyl for epidural analgesia after total knee arthroplasty. Br J Anaesth; 93:670–677.
28. davies, AF, segar, Ep, Murdoch, J, et al (2004). Epidural infusion or combined femoral and sciatic nerve blocks as perioperative analgesia for knee arthroplasty. Br J Anaesth; 93:368–374.
29. Browne, C, Copp, s, reden, L, et al (2004). Bupivacaine bolus injection versus placebo for pain management following total knee arthroplasty. J Arthroplasty; 19:377–380.
13/2009 pAGE – 6
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Tabl
e 1:
Sum
mar
y of
key
ran
dom
ized
con
trol
led
tria
ls o
n th
e m
ultim
odal
app
roac
h to
pai
n m
anag
emen
t
rEFE
rEN
CE
sAM
pLE
TrEA
TMEN
T G
rou
ps A
Nd
pA
iN
MA
NA
GEM
ENT
dET
AiL
sK
Ey r
Esu
LTs
Au
Tho
rs’ C
oN
CLu
sio
Ns
EFFE
CTi
vEN
Ess
oF
TrEA
TMEN
T?*
Kard
ash
et a
l, 20
07 [3
]60
pat
ient
s un
derg
oing
el
ectiv
e un
ilate
ral
tota
l kne
e ar
thro
plas
ty
unde
r spi
nal
anes
thes
ia
In a
rand
omiz
ed, d
oubl
e-bl
ind
man
ner
patie
nts
rece
ived
a fe
mor
al, o
btur
ator
, or
sham
ner
ve b
lock
at t
he e
nd o
f sur
gery
. Bl
ocks
wer
e pe
rform
ed u
sing
ner
ve
stim
ulat
ion
and
20 m
l bup
ivaca
ine
0.5%
co
ntai
ning
epi
neph
rine
5 m
icro
g/m
l. Pa
tient
-con
trolle
d IV
ana
lges
ia w
ith fe
ntan
yl,
cele
coxi
b 10
0 m
g PO
bid
, and
ace
tam
inop
hen
650
mg
PO e
very
6 h
wer
e st
arte
d on
arr
ival
in th
e re
cove
ry ro
om.
Ther
e w
ere
no s
igni
fican
t diff
eren
ces
in th
e ob
tura
tor
bloc
k gr
oup
and
the
cont
rol g
roup
in a
ny o
utco
me
varia
ble.
With
bas
elin
e pa
in s
core
s su
btra
cted
, fe
mor
al b
lock
resu
lted
in le
ss p
ain
at re
st c
ompa
red
with
con
trol a
nd le
ss p
ain
with
mov
emen
t at r
ecov
ery
room
dis
char
ge. N
eith
er b
lock
had
a s
igni
fican
t effe
ct
on o
pioi
d us
e, fu
nctio
nal o
utco
me,
or s
ide
effe
cts.
Fem
oral
ner
ve b
lock
s ra
rely
blo
ck
the
obtu
rato
r ner
ve. S
ingl
e-in
ject
ion
fem
oral
ner
ve b
lock
impr
oved
m
ultim
odal
ana
lges
ia a
fter s
pina
l an
esth
esia
for t
otal
kne
e ar
thro
plas
ty,
but t
his
effe
ct d
id n
ot p
ersi
st b
eyon
d th
e da
y of
sur
gery
.
And
erse
n et
al,
2007
[4]
40 p
atie
nts
unde
rgoi
ng to
tal
hip
repl
acem
ent
Patie
nts
rece
ived
wou
nd in
filtra
tion
at th
e en
d of
sur
gery
and
thro
ugh
an in
traar
ticul
ar
cath
eter
24
h po
stop
erat
ivel
y. T
he c
athe
ter
was
pla
ced
at th
e en
d of
sur
gery
. One
gro
up
rece
ived
sol
utio
ns o
f rop
ivaca
ine,
ket
orol
ac,
and
adre
nalin
e. P
atie
nts
in th
e co
ntro
l gro
up
wer
e in
ject
ed w
ith s
alin
e in
stea
d.
The
patie
nts
who
rece
ived
the
anal
gesi
c so
lutio
n ha
d le
ss p
ain
up to
2 w
eeks
pos
tope
rativ
ely.
The
y re
ache
d an
ear
lier a
nd lo
wer
pai
n m
inim
um d
urin
g th
e fir
st d
ays
post
oper
ativ
ely,
had
low
er u
se o
f an
alge
sia
up to
day
4 p
osto
pera
tivel
y, an
d w
ere
mor
e sa
tisfie
d. U
se o
f ana
lges
ic s
olut
ion
resu
lted
in le
ss jo
int s
tiffn
ess
and
bette
r fun
ctio
n 1 w
eek
post
oper
ativ
ely.
Ope
rativ
e an
d po
stop
erat
ive
wou
nd
infil
tratio
n w
ith m
ultim
odal
dru
gs
redu
ces
pain
and
the
requ
irem
ent
for a
nalg
esic
s af
ter h
ip re
plac
emen
t, le
adin
g to
fast
er p
osto
pera
tive
mob
iliza
tion.
Busc
h et
al,
2006
[5]
64 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
wer
e ra
ndom
ized
eith
er to
rece
ive
a pe
riart
icul
ar in
traop
erat
ive
inje
ctio
n co
ntai
ning
ro
piva
cain
e, k
etor
olac
, epi
mor
phin
e, a
nd
epin
ephr
ine
or to
rece
ive
no in
ject
ion.
Th
e pe
riope
rativ
e an
alge
sic
regi
men
was
st
anda
rdiz
ed. A
ll pa
tient
s in
bot
h gr
oups
re
ceiv
ed p
atie
nt-c
ontro
lled
anal
gesi
a fo
r 24
hour
s af
ter t
he s
urge
ry, a
nd th
is w
as fo
llow
ed
by s
tand
ard
anal
gesi
a.
Patie
nts
who
had
rece
ived
the
inje
ctio
n us
ed
sign
ifica
ntly
less
pat
ient
-con
trolle
d an
alge
sia
at 6
ho
urs,
at 1
2 ho
urs,
and
ove
r the
firs
t 24
hour
s af
ter
the
surg
ery.
The
y ha
d hi
gher
vis
ual a
nalo
g sc
ores
for
patie
nt s
atis
fact
ion
and
low
er v
isua
l ana
log
scor
es
for p
ain
durin
g ac
tivity
in th
e po
st-a
nest
hetic
-car
e un
it an
d 4
hour
s af
ter t
he o
pera
tion.
Intra
oper
ativ
e pe
riart
icul
ar in
ject
ion
with
mul
timod
al d
rugs
can
sig
nific
antly
re
duce
the
requ
irem
ents
for p
atie
nt-
cont
rolle
d an
alge
sia
and
impr
ove
patie
nt s
atis
fact
ion,
with
no
appa
rent
ris
ks, f
ollo
win
g to
tal k
nee
arth
ropl
asty
.
Vend
ittol
i et a
l, 20
06 [6
]42
pat
ient
s un
derg
oing
un
ilate
ral t
otal
kn
ee a
rthr
opla
sty
Patie
nts
wer
e ra
ndom
ized
to re
ceiv
e ei
ther
a
perio
pera
tive
infil
tratio
n m
ixtu
re, c
onsi
stin
g pr
inci
pally
of l
ocal
ane
sthe
tic a
nd s
elf-
adm
inis
tere
d m
orph
ine,
or s
elf-a
dmin
iste
red
mor
phin
e on
ly.
Alth
ough
ther
e w
as h
igh
satis
fact
ion
and
good
pai
n co
ntro
l in
both
gro
ups,
mor
phin
e co
nsum
ptio
n w
as
sign
ifica
ntly
low
er in
the
loca
l ana
lges
ia g
roup
than
it
was
in th
e co
ntro
l gro
up. O
ver t
he 5
-day
per
iod
afte
r th
e pr
oced
ure,
the
patie
nts
in th
e lo
cal a
nalg
esia
gr
oup
repo
rted
a to
tal o
f 2.6
+/–
3.9
hou
rs o
f nau
sea
com
pare
d w
ith 7
.1 +/
– 12
.2 h
ours
in th
e co
ntro
l gr
oup.
This
mul
timod
al p
erio
pera
tive
anal
gesi
a pr
otoc
ol th
at in
clud
ed in
filtra
tion
of
a lo
cal a
nest
hetic
offe
red
impr
oved
pa
in c
ontro
l and
min
imal
sid
e ef
fect
s to
pat
ient
s un
derg
oing
tota
l kne
e ar
thro
plas
ty.
Barr
ingt
on e
t al,
2005
[7]
108
patie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
unde
rgoi
ng to
tal k
nee
repl
acem
ent
unde
r spi
nal a
nest
hesi
a w
ere
rand
omiz
ed
to re
ceiv
e ei
ther
a fe
mor
al in
fusi
on o
f bu
piva
cain
e 0.
2% (m
edia
n in
fusi
on ra
te
9.3
ml/h
) or a
n ep
idur
al in
fusi
on o
f ro
piva
cain
e 0.
2% w
ith fe
ntan
yl 4
mic
rog/
ml
(med
ian
infu
sion
rate
7.6
ml/h
). A
djuv
ant
anal
gesi
cs w
ere
oral
rofe
coxi
b an
d ox
ycod
one
and
IV m
orph
ine.
Ther
e w
ere
equi
vale
nt p
ain
scor
es, r
ange
of
mov
emen
t, an
d re
habi
litat
ion
in b
oth
grou
ps. T
here
w
as s
igni
fican
tly le
ss n
ause
a an
d vo
miti
ng in
the
cont
inuo
us fe
mor
al n
erve
blo
ckad
e gr
oup.
The
co
ntin
uous
fem
oral
ner
ve b
lock
ade
grou
p re
ceiv
ed
mor
e ro
feco
xib
and
oxyc
odon
e th
an th
e co
ntin
uous
ep
idur
al a
nalg
esia
gro
up.
Cont
inuo
us fe
mor
al n
erve
blo
ckad
e is
an
effe
ctiv
e re
gion
al c
ompo
nent
of a
m
ultim
odal
ana
lges
ic s
trate
gy a
fter t
otal
kn
ee re
plac
emen
t.
13/2009 pAGE – 7
JointEvidence The multimodal pain management approach in total knee arthroplasty
JointEvidence
K_JE_PainManagement_TKA_08.indd 7 26.3.2009 17:49:51 Uhr
rEFE
rEN
CE
sAM
pLE
TrEA
TMEN
T G
rou
ps A
Nd
pA
iN
MA
NA
GEM
ENT
dET
AiL
sK
Ey r
Esu
LTs
Au
Tho
rs’ C
oN
CLu
sio
Ns
EFFE
CTi
vEN
Ess
oF
TrEA
TMEN
T?*
Buva
nend
ran
et
al, 2
003
[8]
70 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
wer
e ra
ndom
ly a
ssig
ned
to re
ceiv
e 50
mg
of o
ral r
ofec
oxib
at 2
4 ho
urs
and
at 1
to 2
hou
rs b
efor
e TK
A, 5
0 m
g da
ily fo
r 5 d
ays
post
oper
ativ
ely,
and
25 m
g da
ily fo
r ano
ther
8
days
, or m
atch
ing
plac
ebo
at th
e sa
me
times
.
Tota
l epi
dura
l ana
lges
ic c
onsu
mpt
ion
and
in-h
ospi
tal
opio
id c
onsu
mpt
ion
wer
e le
ss in
the
grou
p re
ceiv
ing
rofe
coxi
b co
mpa
red
with
the
grou
p re
ceiv
ing
plac
ebo.
Med
ian
pain
sco
re a
chie
ved
for t
he k
nee
was
low
er in
the
rofe
coxi
b gr
oup
com
pare
d w
ith th
e pl
aceb
o gr
oup
durin
g ho
spita
l sta
y an
d 1 w
eek
afte
r di
scha
rge.
The
re w
as le
ss p
osto
pera
tive
vom
iting
in
the
rofe
coxi
b gr
oup
(6%
) com
pare
d w
ith th
e pl
aceb
o gr
oup
(26%
). Kn
ee fl
exio
n w
as in
crea
sed
in th
e ro
feco
xib
grou
p co
mpa
red
with
the
plac
ebo
grou
p at
dis
char
ge a
nd a
t 1 m
onth
pos
tope
rativ
ely,
with
sh
orte
r tim
e in
phy
sica
l the
rapy
to a
chie
ve e
ffect
ive
join
t ran
ge o
f mot
ion.
Perio
pera
tive
use
of a
n in
hibi
tor o
f cy
cloo
xyge
nase
2 is
an
effe
ctiv
e co
mpo
nent
of m
ultim
odal
ana
lges
ia
that
redu
ces
opio
id c
onsu
mpt
ion,
pai
n,
vom
iting
, and
sle
ep d
istu
rban
ce, w
ith
impr
oved
kne
e ra
nge
of m
otio
n af
ter
tota
l kne
e ar
thro
plas
ty.
Cam
u et
al,
2002
[9
]19
5 pa
tient
s un
derg
oing
tota
l hi
p re
plac
emen
t
This
stu
dy c
ompa
red
the
opio
id-s
parin
g ef
fect
s, a
nalg
esic
effi
cacy
, and
saf
ety
of 2
0-
and
40-m
g do
ses
of v
alde
coxi
b tw
ice
daily
w
ith p
lace
bo in
pat
ient
s re
ceiv
ing
mor
phin
e by
pat
ient
-con
trolle
d an
alge
sia
afte
r hip
ar
thro
plas
ty. S
tudy
med
icat
ion
was
firs
t ad
min
iste
red
1 to
3 ho
urs
preo
pera
tivel
y.
Patie
nts
rece
ivin
g 20
or 4
0 m
g va
ldec
oxib
twic
e da
ily
requ
ired
on a
vera
ge 4
0% le
ss m
orph
ine
than
thos
e re
ceiv
ing
plac
ebo
afte
r hip
art
hrop
last
y. P
ain
inte
nsity
le
vels
and
pat
ient
sat
isfa
ctio
n w
ere
sign
ifica
ntly
im
prov
ed in
bot
h va
ldec
oxib
gro
ups
com
pare
d w
ith
plac
ebo.
Val
deco
xib
and
plac
ebo
wer
e eq
ually
wel
l to
lera
ted.
Pre-
and
pos
tope
rativ
e ad
min
istra
tion
of v
alde
coxi
b re
duce
s th
e am
ount
of
mor
phin
e re
quire
d fo
r pos
tope
rativ
e pa
in re
lief a
nd p
rovi
des
grea
ter
anal
gesi
c ef
ficac
y co
mpa
red
with
m
orph
ine
alon
e.
Ada
m e
t al,
2005
[1
0]40
pat
ient
s un
derg
oing
tota
l kn
ee a
rthr
opla
sty
Patie
nts
wer
e ra
ndom
ly a
ssig
ned
to re
ceiv
e an
initi
al b
olus
of 0
.5 m
g/kg
ket
amin
e fo
llow
ed b
y a
cont
inuo
us in
fusi
on o
f 3 m
ug
. kg(
-1) .
min
(-1) d
urin
g su
rger
y an
d 1.5
mug
. k
g(-1
) . m
in(-1
) for
48
h (k
etam
ine
grou
p) o
r an
equ
al v
olum
e of
sal
ine
(con
trol g
roup
). A
dditi
onal
pos
tope
rativ
e an
alge
sia
was
pr
ovid
ed b
y pa
tient
-con
trolle
d IV
mor
phin
e.
The
keta
min
e gr
oup
requ
ired
sign
ifica
ntly
less
m
orph
ine
than
the
cont
rol g
roup
. Pat
ient
s in
the
keta
min
e gr
oup
reac
hed
90°
of a
ctiv
e kn
ee fl
exio
n m
ore
rapi
dly
than
thos
e in
the
cont
rol.
Out
com
es a
t 6
wee
ks a
nd 3
mon
ths
wer
e si
mila
r in
each
gro
up.
Thes
e re
sults
con
firm
that
ket
amin
e is
a u
sefu
l ana
lges
ic a
djuv
ant i
n pe
riope
rativ
e m
ultim
odal
ana
lges
ia
with
a p
ositi
ve im
pact
on
early
kne
e m
obili
zatio
n.
Stille
r et a
l, 20
07
[11]
63 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
wer
e ra
ndom
ized
to re
ceiv
e sa
line
or tr
amad
ol 10
0 m
g/m
l int
rave
nous
ly e
very
6
h du
ring
the
first
pos
tope
rativ
e da
y (to
tal,
400
mg/
24 h
). A
ll pa
tient
s ha
d ac
cess
to
mor
phin
e vi
a a
patie
nt-c
ontro
lled
anal
gesi
a pu
mp.
Ther
e w
as n
o di
ffere
nce
with
in th
e fir
st p
osto
pera
tive
day
with
rega
rd to
pai
n in
tens
ity, s
edat
ion
and
naus
ea b
etw
een
patie
nts
treat
ed w
ith tr
amad
ol a
nd
the
plac
ebo
grou
p. T
he w
ithdr
awal
rate
cau
sed
by
insu
ffici
ent p
ain
relie
f was
gre
ater
in th
e tra
mad
ol
grou
p (7
/31)
than
in th
e sa
line
grou
p (2
/32)
. In
the
grou
p of
pat
ient
s w
ho re
mai
ned
in th
e st
udy
for 2
4 ho
urs,
thos
e ra
ndom
ized
to re
ceiv
e tra
mad
ol h
ad
sign
ifica
ntly
low
er m
orph
ine
cons
umpt
ion
than
the
plac
ebo
grou
p.
This
stu
dy d
oes
not s
uppo
rt th
e co
mbi
natio
n of
tram
adol
and
mor
phin
e vi
a pa
tient
-con
trolle
d an
alge
sia
for
post
oper
ativ
e pa
in re
lief a
fter p
rimar
y to
tal k
nee
arth
ropl
asty
.
Parv
atan
eni e
t al,
2007
[12]
131 p
atie
nts
unde
rgoi
ng
tota
l hip
or k
nee
arth
ropl
asty
Patie
nts
wer
e ra
ndom
ized
to e
ither
a s
tudy
gr
oup
rece
ivin
g pe
riart
icul
ar in
ject
ions
or a
co
ntro
l gro
up re
ceiv
ing
patie
nt-c
ontro
lled
anal
gesi
a w
ith o
r with
out f
emor
al n
erve
blo
ck
(tota
l kne
e pa
tient
s). A
ll pa
tient
s re
ceiv
ed
a co
mpr
ehen
sive
mul
timod
al p
erio
pera
tive
prot
ocol
.
The
tota
l hip
art
hrop
last
y st
udy
grou
p de
mon
stra
ted
sign
ifica
ntly
low
er a
vera
ge p
ain
scor
es a
nd h
ighe
r ov
eral
l sat
isfa
ctio
n th
an th
e co
ntro
l gro
up. T
here
was
no
sig
nific
ant d
iffer
ence
in p
ain
scor
es b
etw
een
the
stud
y an
d co
ntro
l gro
ups
in th
e to
tal k
nee
coho
rt.
Both
stu
dy g
roup
s de
mon
stra
ted
low
er n
arco
tic
usag
e an
d si
de e
ffect
s as
wel
l as
impr
oved
ear
ly
func
tiona
l rec
over
y.
Peria
rtic
ular
inje
ctio
n w
ith a
mul
timod
al
prot
ocol
was
sho
wn
to s
afel
y pr
ovid
e ex
celle
nt p
ain
cont
rol a
nd fu
nctio
nal
reco
very
and
can
be
subs
titut
ed fo
r co
nven
tiona
l pai
n co
ntro
l mod
aliti
es.
13/2009 pAGE – 8
JointEvidence The multimodal pain management approach in total knee arthroplasty
JointEvidence
K_JE_PainManagement_TKA_08.indd 8 26.3.2009 17:49:51 Uhr
rEFE
rEN
CE
sAM
pLE
TrEA
TMEN
T G
rou
ps A
Nd
pA
iN
MA
NA
GEM
ENT
dET
AiL
sK
Ey r
Esu
LTs
Au
Tho
rs’ C
oN
CLu
sio
Ns
EFFE
CTi
vEN
Ess
oF
TrEA
TMEN
T?*
Long
et a
l, 20
06
[13]
70 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
rece
ived
the
sam
e po
stop
erat
ive
pain
man
agem
ent p
lan,
with
the
exce
ptio
n of
rand
om a
ssig
nmen
t to
eith
er c
ontin
uous
ep
idur
al c
athe
ter o
r con
tinuo
us fe
mor
al
nerv
e ca
thet
er in
fusi
on fo
r 36
hour
s po
st-
oper
ativ
ely.
The
fem
oral
cat
hete
r gro
up h
ad le
ss p
ain
on d
ay
0 an
d da
y 1 c
ompa
red
to th
e ep
idur
al g
roup
. The
fe
mor
al c
athe
ter g
roup
con
sum
ed le
ss m
orph
ine
on
day
1 com
pare
d to
the
epid
ural
gro
up.
The
cont
inuo
us fe
mor
al c
athe
ter
prov
ided
sup
erio
r pai
n re
lief c
ompa
red
to th
e co
ntin
uous
epi
dura
l cat
hete
r.
Kim
et a
l, 20
07
[14]
50 p
atie
nts
unde
rgoi
ng
unila
tera
l to
tal k
nee
repl
acem
ent
Patie
nts
wer
e ra
ndom
ly a
ssig
ned
to re
ceiv
e ei
ther
suf
enta
nil i
n ro
piva
cain
e al
one
(gro
up
C) o
r the
sam
e so
lutio
n w
ith n
alox
one
(gro
up
N) f
or th
eir p
osto
pera
tive
epid
ural
ana
lges
ia.
The
naus
ea s
core
in g
roup
N w
as s
igni
fican
tly lo
wer
th
an th
at in
gro
up C
. The
VA
S pa
in s
core
at r
est a
nd
on m
ovem
ent w
ere
sign
ifica
ntly
low
er in
gro
up N
th
an in
gro
up C
at 2
4 h.
Oth
er o
pioi
d-in
duce
d si
de-
effe
cts
wer
e no
t sig
nific
antly
diff
eren
t.
Epid
ural
nal
oxon
e w
as e
ffect
ive
in
redu
cing
pos
tope
rativ
e na
usea
and
vo
miti
ng in
duce
d by
epi
dura
l suf
enta
nil
and
addi
tiona
lly e
nhan
ced
the
anal
gesi
c ef
fect
. The
refo
re, c
onco
mita
nt
infu
sion
of a
sm
all d
ose
of e
pidu
ral
nalo
xone
sho
uld
be c
onsi
dere
d to
re
duce
pos
tope
rativ
e na
usea
and
vo
miti
ng, e
spec
ially
in p
atie
nts
at
grea
ter r
isk
for p
osto
pera
tive
naus
ea
and
vom
iting
.
Han
et a
l, 20
07
[15]
90 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
wer
e ra
ndom
ly d
ivid
ed in
to th
ree
equa
l gro
ups.
Bef
ore
wou
nd c
losu
re, p
atie
nts
wer
e gi
ven
intra
syno
vial
inje
ctio
ns o
f the
fo
llow
ing
solu
tions
: pat
ient
s in
gro
up I
rece
ived
40
ml o
f 300
mg
ropi
vaca
ine
with
1:2
00,0
00 e
pine
phrin
e an
d 5
mg
mor
phin
e;
patie
nts
in G
roup
II re
ceiv
ed 4
0 m
l of 3
00 m
g ro
piva
cain
e w
ith e
pine
phrin
e; a
nd p
atie
nts
in G
roup
III r
ecei
ved
50 m
l nor
mal
sal
ine
as
a co
ntro
l. A
ll pa
tient
s re
ceiv
ed a
n ep
idur
al
patie
nt-c
ontro
lled
anal
gesi
a (P
CA) f
or 2
4 po
stop
erat
ive
hour
s.
Ther
e w
ere
no s
igni
fican
t diff
eren
ces
amon
g th
e th
ree
grou
ps w
ith re
gard
s to
the
VAS
and
the
requ
ired
dose
of r
escu
e an
alge
sia.
Non
e of
the
grou
ps d
emon
stra
ted
sign
ifica
nt d
iffer
ence
s in
th
e ra
nge
of k
nee
flexi
on a
nd th
e in
cide
nce
of
post
oper
ativ
e na
usea
and
em
esis
.
The
auth
ors
foun
d th
at ro
piva
cain
e,
alon
e or
with
mor
phin
e, in
ject
ed in
to
the
syno
vial
tiss
ue, a
long
with
an
epid
ural
PCA
has
no
addi
tiona
l ben
efits
in
pai
n co
ntro
l afte
r a to
tal k
nee
arth
ropl
asty
.
Toftd
ahl e
t al,
2007
[16]
80 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
who
rece
ived
spi
nal a
nest
hesi
a w
ere
rand
omiz
ed to
rece
ive
cont
inuo
us
fem
oral
ner
ve b
lock
(gro
up F
) or p
eri-
and
intra
artic
ular
infil
tratio
n an
d in
ject
ion
(gro
up
I). G
roup
I re
ceiv
ed a
sol
utio
n of
300
mg
ropi
vaca
ine,
30
mg
keto
rola
c, a
nd 0
.5 m
g ep
inep
hrin
e by
infil
tratio
n of
the
knee
at t
he
end
of s
urge
ry, a
nd 2
pos
tope
rativ
e in
ject
ions
of
thes
e su
bsta
nces
thro
ugh
an in
traar
ticul
ar
cath
eter
.
Mor
e pa
tient
s in
gro
up I
than
in g
roup
F c
ould
wal
k <
3 m
on
the
first
pos
tope
rativ
e da
y (2
9/39
vs
7/37
, p
<0.
001).
Gro
up I
also
had
sig
nific
antly
low
er p
ain
scor
es d
urin
g ac
tivity
and
low
er c
onsu
mpt
ion
of
opio
ids
on th
e fir
st p
osto
pera
tive
day.
No
diffe
renc
es
betw
een
grou
ps w
ere
seen
rega
rdin
g si
de e
ffect
s or
le
ngth
of s
tay.
Peri-
and
intra
artic
ular
app
licat
ion
of a
nalg
esic
s by
infil
tratio
n an
d bo
lus
inje
ctio
ns c
an im
prov
e ea
rly
anal
gesi
a an
d m
obili
zatio
n fo
r pat
ient
s un
derg
oing
tota
l kne
e ar
thro
plas
ty.
Furt
her s
tudi
es o
f opt
imal
dru
gs,
dosa
ge, a
nd d
urat
ion
of th
is tr
eatm
ent
are
war
rant
ed.
13/2009 pAGE – 9
JointEvidence The multimodal pain management approach in total knee arthroplasty
JointEvidence
K_JE_PainManagement_TKA_08.indd 9 26.3.2009 17:49:51 Uhr
rEFE
rEN
CE
sAM
pLE
TrEA
TMEN
T G
rou
ps A
Nd
pA
iN
MA
NA
GEM
ENT
dET
AiL
sK
Ey r
Esu
LTs
Au
Tho
rs’ C
oN
CLu
sio
Ns
EFFE
CTi
vEN
Ess
oF
TrEA
TMEN
T?*
Inan
et a
l, 20
07
[17]
46 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
In th
is d
oubl
e-bl
ind,
rand
omiz
ed, p
lace
bo
cont
rolle
d st
udy,
the
effe
ct o
f lor
noxi
cam
ad
min
istra
tion
(32
mg/
48 h
our)
on m
orph
ine
cons
umpt
ion
and
drug
-rel
ated
sid
e ef
fect
s w
ere
inve
stig
ated
in e
lder
ly p
atie
nts
unde
rgoi
ng to
tal k
nee
repl
acem
ent.
Gro
up
M a
nd g
roup
L re
ceiv
ed m
orph
ine
with
pa
tient
con
trolle
d an
alge
sia
(PCA
) dev
ice
post
oper
ativ
ely.
Add
ition
ally
gro
up L
rece
ived
lo
rnox
icam
16 m
g in
trave
nous
ly 15
min
utes
be
fore
sur
gery
and
8 m
g at
pos
tope
rativ
e 12
th
and
24th
hou
rs.
At t
he e
nd o
f 48t
h ho
ur, m
ean
tota
l mor
phin
e co
nsum
ptio
ns (m
ean
+/-
SD) f
or g
roup
M a
nd g
roup
L
wer
e 63
.70
+/-1
5.7
0 m
g an
d 34
.60
+/-
16.3
2 m
g,
resp
ectiv
ely.
AUC
(are
a un
der t
he c
urve
) mor
phin
e 0–
48h
in g
roup
M w
as 5
9 +/
- 13
and
in g
roup
L it
w
as 3
0+/-
13 (P
<0.
001).
Inci
denc
e of
sid
e ef
fect
s in
gr
oup
M w
ere
60%
and
25%
in g
roup
L (P
<0.
05).
In g
roup
M, 8
pat
ient
s (4
0%) e
xper
ienc
ed n
ause
a an
d 3
(15%
) pat
ient
s ex
perie
nced
itch
ing
whe
re a
s in
gro
up L
, 3 p
atie
nts
(15%
) exp
erie
nced
nau
sea,
1 pa
tient
(5%
) itc
hing
, 1 p
atie
nt (5
%) d
ry m
outh
.
Lorn
oxic
am a
dmin
istra
tion
in to
tal
knee
repl
acem
ent i
s as
soci
ated
with
de
crea
sed
mor
phin
e co
nsum
ptio
n fo
r po
stop
erat
ive
anal
gesi
a an
d fe
wer
sid
e ef
fect
s.
Chu
et a
l, 20
06
[18]
60 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
wer
e ra
ndom
ized
to e
ither
gen
eral
an
esth
esia
follo
wed
by
post
oper
ativ
e in
trave
nous
pat
ient
-con
trolle
d an
alge
sia
with
mor
phin
e, o
r com
bine
d sp
inal
-epi
dura
l an
esth
esia
follo
wed
by
post
oper
ativ
e ep
idur
al
infu
sion
of b
upiva
cain
e 0.
1% w
ith fe
ntan
yl 2
m
icro
g/m
l.
Post
oper
ativ
e m
edia
n pa
in s
core
s w
ere
cons
iste
ntly
lo
wer
at 1
(P <
0.00
01),
6 (P
= 0
.08)
, 12
(P =
0.0
03),
24
(P =
0.14
), an
d 48
hou
rs (P
= 0
.007
) in
thos
e pa
tient
s gi
ven
regi
onal
ana
esth
esia
. Alth
ough
ther
e w
as a
tre
nd to
war
ds fe
wer
com
plic
atio
ns in
the
latte
r gro
up,
ther
e w
ere
no s
tatis
tical
ly s
igni
fican
t diff
eren
ces
betw
een
the
two
grou
ps w
ith re
spec
t to
the
inci
denc
e of
pos
tope
rativ
e bl
ood
loss
, hem
odyn
amic
in
stab
ility
, pru
ritus
, nau
sea,
vom
iting
, urin
ary
rete
ntio
n, o
r oth
er s
urgi
cal/m
edic
al c
ompl
icat
ions
. Po
stop
erat
ivel
y, pa
tient
s gi
ven
regi
onal
ane
sthe
sia
also
resu
med
mea
ls e
arlie
r (P
<0.
0001
), an
d sh
owed
a
trend
tow
ards
ear
lier a
mbu
latio
n an
d ho
spita
l di
scha
rge.
Patie
nts
unde
rgoi
ng to
tal k
nee
arth
ropl
asty
with
regi
onal
ane
sthe
sia/
re
gion
ally
del
iver
ed a
nalg
esia
enj
oyed
be
tter p
osto
pera
tive
pain
relie
f and
re
sum
ed m
eals
ear
lier t
han
thos
e re
ceiv
ing
gene
ral a
nest
hesi
a/
intra
veno
us p
atie
nt-c
ontro
lled
anal
gesi
a.
Zaric
et a
l, 20
06
[19]
60 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
wer
e pr
ospe
ctiv
ely
rand
omiz
ed to
re
ceiv
e ei
ther
epi
dura
l inf
usio
n or
com
bine
d co
ntin
uous
fem
oral
and
sci
atic
ner
ve b
lock
s.
Ropi
vaca
ine
2 m
g/m
l plu
s su
fent
anil
1 m
ug/m
l was
giv
en e
ither
epi
dura
lly o
r th
roug
h th
e fe
mor
al n
erve
cat
hete
r, an
d ro
piva
cain
e 0.
5 m
g/m
l was
giv
en th
roug
h th
e sc
iatic
ner
ve c
athe
ter u
sing
ela
stom
eric
in
fuse
rs (d
eliv
erin
g 5
ml/h
for 5
5 h)
.
One
or m
ore
side
effe
cts
wer
e pr
esen
t in
87%
of
patie
nts
in th
e ep
idur
al g
roup
whe
reas
onl
y 35
% o
f pa
tient
s in
the
fem
oral
and
sci
atic
blo
ck g
roup
s w
ere
affe
cted
on
the
first
pos
tope
rativ
e da
y (P
= 0
.000
2).
Mot
or b
lock
ade
was
mor
e in
tens
e in
the
oper
ated
lim
b on
the
day
of s
urge
ry a
nd th
e fir
st p
osto
pera
tive
day
in th
e pe
riphe
ral n
erve
blo
ck g
roup
(P =
0.0
01),
whe
reas
the
nono
pera
ted
limb
was
mor
e bl
ocke
d in
th
e ep
idur
al g
roup
on
the
day
of s
urge
ry
(P =
0.0
003)
.
The
resu
lts d
emon
stra
te a
redu
ced
inci
denc
e of
sid
e ef
fect
s in
the
fem
oral
/sci
atic
ner
ve b
lock
gro
up
than
in th
e ep
idur
al g
roup
on
the
first
po
stop
erat
ive
day.
13/2009 pAGE – 10
JointEvidence The multimodal pain management approach in total knee arthroplasty
JointEvidence
K_JE_PainManagement_TKA_08.indd 10 26.3.2009 17:49:51 Uhr
rEFE
rEN
CE
sAM
pLE
TrEA
TMEN
T G
rou
ps A
Nd
pA
iN
MA
NA
GEM
ENT
dET
AiL
sK
Ey r
Esu
LTs
Au
Tho
rs’ C
oN
CLu
sio
Ns
EFFE
CTi
vEN
Ess
oF
TrEA
TMEN
T?*
Seet
et a
l, 20
06
[20]
60 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
unde
rgoi
ng e
lect
ive
unila
tera
l tot
al
knee
art
hrop
last
y un
der s
ubar
achn
oid
bloc
k w
ere
rand
omiz
ed in
to th
ree
grou
ps.
Post
oper
ativ
e an
alge
sia
was
pro
vide
d w
ith a
co
ntin
uous
3-in
-1 fe
mor
al n
erve
cat
hete
r with
0.
15%
ropi
vaca
ine
in g
roup
A, a
con
tinuo
us
3-in
-1 fe
mor
al n
erve
cat
hete
r with
0.2
%
ropi
vaca
ine
in g
roup
B, o
r pat
ient
con
trolle
d in
trave
nous
mor
phin
e in
gro
up C
(con
trol
grou
p). G
roup
s A
and
B re
ceiv
ed p
atie
nt
cont
rolle
d in
trave
nous
mor
phin
e pu
mps
for
resc
ue a
nalg
esia
.
Ther
e w
as n
o st
atis
tical
diff
eren
ce in
pai
n sc
ore
betw
een
the
grou
ps. T
otal
mor
phin
e us
e w
as h
ighe
st
in g
roup
C (P
<0.
05).
No
appr
ecia
ble
diffe
renc
e co
uld
be fo
und
with
sen
sorim
otor
blo
ckad
e, m
orph
ine
usag
e an
d sa
tisfa
ctio
n sc
ores
whe
n co
mpa
ring
grou
ps A
and
B. F
emor
al c
athe
ter d
islo
dgem
ent
rate
was
7.9
%. T
here
was
no
stat
istic
al d
iffer
ence
be
twee
n th
e gr
oups
whe
n co
mpa
ring
the
day
of
first
am
bula
tion
and
the
time
to d
isch
arge
from
the
hosp
ital.
Satis
fact
ion
scor
es w
ere
high
er in
gro
up
A (P
= 0
.028
) and
gro
up B
(P =
0.0
02) c
ompa
red
to
grou
p C.
The
auth
ors
conc
lude
d th
at a
co
ntin
uous
3-in
-1 fe
mor
al n
erve
bl
ock
with
ropi
vaca
ine
0.15
% o
r 0.
2% fo
r ele
ctiv
e un
ilate
ral t
otal
kne
e ar
thro
plas
ty h
as a
n op
ioid
-spa
ring
effe
ct.
Case
y et
al,
2006
[2
1]40
pat
ient
s un
derg
oing
tota
l kn
ee a
rthr
opla
sty
Patie
nts
wer
e ra
ndom
ized
to re
ceiv
e ca
psul
es
cont
aini
ng e
ither
nim
odip
ine
30 m
g or
pl
aceb
o in
a d
oubl
e-bl
ind
stud
y de
sign
. All
patie
nts
rece
ived
3 c
apsu
les
(nim
odip
ine
90 m
g or
pla
cebo
) 1–2
h b
efor
e in
duct
ion
of a
nest
hesi
a fo
llow
ed b
y or
al n
imod
ipin
e 30
mg
or p
lace
bo 6
hou
rly fo
r 48
hour
s po
stop
erat
ivel
y. S
pina
l ane
sthe
sia
was
in
duce
d w
ith h
yper
baric
bup
ivaca
ine
0.5%
(2
.4) 3
.0 m
l, an
d flu
ids
and
ephe
drin
e w
ere
give
n at
the
disc
retio
n of
the
anes
thes
iolo
gist
. M
orph
ine
patie
nt-c
ontro
lled
anal
gesi
a (P
CA,
bolu
s 1 m
g, lo
ckou
t 5 m
in) w
as g
iven
for
post
oper
ativ
e an
alge
sia.
Mor
phin
e co
nsum
ptio
n w
as s
igni
fican
tly la
rger
in
nim
odip
ine
patie
nts
at 12
h (3
9 +/
– 18
ver
sus
29
+/–
15; P
= 0
.04)
, 24
h (6
2 +/
– 23
ver
sus
45
+/–
24;
P =
0.0
2), a
nd 4
8 h
(88
+/–
34 v
ersu
s 61
+/–
27;
P =
0.0
1). T
here
wer
e no
sig
nific
ant
diffe
renc
es in
pai
n sc
ores
at r
est o
r mov
ing,
or i
n
time
to fi
rst u
se o
f mor
phin
e an
alge
sia.
This
stu
dy h
as d
emon
stra
ted
incr
ease
d m
orph
ine
cons
umpt
ion
afte
r 12
h in
pos
tope
rativ
e pa
tient
s re
ceiv
ing
nim
odip
ine,
sug
gest
ing
that
, in
patie
nts
unde
rgoi
ng k
nee
repl
acem
ent s
urge
ry,
it ha
s no
adj
unct
ive
anal
gesi
c ef
fect
an
d m
ay a
ctua
lly in
hibi
t the
ana
lges
ic
effe
ct o
f mor
phin
e.
Axe
lsso
n et
al,
2005
[22]
45 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Post
oper
ativ
e pa
in re
lief w
ith a
com
bina
tion
of e
pidu
ral r
opiva
cain
e (g
roup
L: 1
0 m
g h-
1, gr
oup
H: 1
6 m
g h-
1) an
d m
orph
ine
(0.16
mg
h-1)
was
eva
luat
ed in
30
patie
nts.
A p
lace
bo
grou
p (g
roup
PL)
of 1
5 pa
tient
s ha
ving
PCA
m
orph
ine
serv
ed a
s th
e co
ntro
l.
VAS
scor
es a
t res
t wer
e si
gnifi
cant
ly lo
wer
in g
roup
s L
and
H c
ompa
red
to g
roup
PL.
On
mov
emen
t, gr
oup
H h
ad lo
wer
VA
S sc
ores
than
gro
up P
L du
ring
3–27
h
(P <
0.05
) and
gro
up L
dur
ing
4–9
h (P
<0.
05),
whi
le
grou
p L
had
a lo
wer
VA
S th
an g
roup
PL
durin
g 9–
18 h
(P
<0.
05).
Mor
phin
e co
nsum
ptio
n af
ter 4
8 h
was
gr
eate
r in
grou
p PL
(64.
6 +/
– 36
.3 m
g) v
s. g
roup
L
(23.
3 +/
– 33
.9 m
g) (P
<0.
001)
and
grou
p H
(4
.3 +
/– 9
.6 m
g) (P
<0.
0001
). M
ild m
otor
blo
ck w
as
seen
in g
roup
H in
20%
and
14%
of p
atie
nts
at 2
4 h
an
d 48
h, r
espe
ctiv
ely,
but t
ime
to m
obili
zatio
n w
as
sim
ilar b
etw
een
the
grou
ps. P
rurit
us w
as m
ore
com
mon
in th
e ro
piva
cain
e gr
oups
(P <
0.05
).
Lum
bar e
pidu
ral a
nalg
esia
usi
ng a
co
mbi
natio
n of
ropi
vaca
ine
(16 m
g h-
1) an
d m
orph
ine
(0.16
mg
h-1)
prov
ides
su
perio
r ana
lges
ia c
ompa
red
to th
e PC
A te
chni
que
or ro
piva
cain
e (10
mg
h-1)
and
mor
phin
e (0
.16 m
g h-
1).
13/2009 pAGE – 11
JointEvidence The multimodal pain management approach in total knee arthroplasty
JointEvidence
K_JE_PainManagement_TKA_08.indd 11 26.3.2009 17:49:52 Uhr
rEFE
rEN
CE
sAM
pLE
TrEA
TMEN
T G
rou
ps A
Nd
pA
iN
MA
NA
GEM
ENT
dET
AiL
sK
Ey r
Esu
LTs
Au
Tho
rs’ C
oN
CLu
sio
Ns
EFFE
CTi
vEN
Ess
oF
TrEA
TMEN
T?*
YaD
eau
et a
l, 20
05 [2
3]80
pat
ient
s un
derg
oing
tota
l kn
ee a
rthr
opla
sty
Forty
-one
pat
ient
s re
ceiv
ed a
sin
gle-
inje
ctio
n fe
mor
al n
erve
blo
ck w
ith 0
.375
% b
upiva
cain
e an
d 5
mic
rog/
mL
epin
ephr
ine;
39
patie
nts
serv
ed a
s co
ntro
ls. A
ll pa
tient
s re
ceiv
ed
com
bine
d sp
inal
-epi
dura
l ane
sthe
sia
and
patie
nt-c
ontro
lled
epid
ural
ana
lges
ia
with
0.0
6% b
upiva
cain
e an
d 10
mic
rog/
ml
hydr
omor
phon
e. A
vera
ge d
urat
ion
of e
pidu
ral
anal
gesi
a w
as 2
day
s.
Med
ian
visu
al a
nalo
g sc
ale
scor
es w
ith p
hysi
cal
ther
apy
wer
e si
gnifi
cant
ly lo
wer
for 2
day
s am
ong
patie
nts
who
rece
ived
a fe
mor
al n
erve
blo
ck v
ersu
s co
ntro
ls: 3
ver
sus
4 (d
ay 1)
, 2.5
ver
sus
4 (d
ay 2
);
P <
0.05
. Med
ian
VAS
pain
sco
res
at re
st w
ere
0 in
bo
th g
roup
s on
day
s 1 a
nd 2
. Fle
xion
rang
e of
mot
ion
was
impr
oved
on
post
oper
ativ
e da
y 2
(70°
ver
sus
63°
; P <
0.05
).
The
auth
ors
conc
lude
that
the
addi
tion
of fe
mor
al n
erve
blo
ckad
e to
epi
dura
l an
alge
sia
sign
ifica
ntly
impr
oved
an
alge
sia
for t
he fi
rst 2
day
s af
ter t
otal
kn
ee a
rthr
opla
sty.
Nec
hleb
a et
al,
2005
[24]
30 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
rand
omly
rece
ived
eith
er 0
.25%
bu
piva
cain
e or
nor
mal
sal
ine
by lo
cal i
nfus
ion
pum
p. S
tand
ard
wou
nd d
rain
age
also
was
im
plem
ente
d.
Mea
n pr
eope
rativ
e vi
sual
ana
log
scor
es w
ere
sim
ilar
betw
een
the
salin
e an
d bu
piva
cain
e gr
oups
(6
.5 +
/– 1.
4 an
d 6.
1 +/–
2.0
, res
pect
ivel
y; P
= .5
35).
By th
e en
d of
the
seco
nd p
osto
pera
tive
day,
scor
es
decr
ease
d to
3.4
+/–
3.2
for t
he s
alin
e gr
oup
and
2.5
+/–
1.6 fo
r the
bup
ivaca
ine
grou
p. M
ean
narc
otic
de
man
d an
d us
age
wer
e 87
+/–
114.
1 req
uest
s w
ith
usag
e of
11.8
+/–
12.3
mg
for t
he s
alin
e gr
oup
and
96
+/–
104.
8 re
ques
ts w
ith u
sage
of 7
.5 +
/– 3
.8 m
g fo
r the
bup
ivaca
ine
grou
p (P
= .5
05).
Thes
e fin
ding
s su
gges
t con
tinuo
us
loca
l ana
lges
ic in
fusi
on a
fter t
otal
kne
e ar
thro
plas
ty d
oes
not o
ffer s
igni
fican
t im
prov
emen
ts in
eith
er p
ain
relie
f or
med
icat
ion
use.
Fara
g et
al,
2005
[25]
38 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
One
gro
up re
ceiv
ed s
pina
l ane
sthe
sia
with
0.5
% b
upiva
cain
e an
d an
alge
sia
with
in
trave
nous
pat
ient
-con
trolle
d an
alge
sia
mor
phin
e, d
eman
d m
ode
only.
The
oth
er
grou
p w
as g
iven
epi
dura
l ane
sthe
sia
with
1.0
% ro
piva
cain
e w
ith 1:
200,
000
epin
ephr
ine
and
anal
gesi
a w
ith 0
.2%
ropi
vaca
ine
at
8 m
l/h, m
aint
aine
d fo
r 7 d
ays.
Bot
h gr
oups
ha
d co
mpr
essi
on s
tock
ing
for d
eep
veno
us
thro
mbo
sis
(DVT
) pro
phyl
axis
, urin
ary
cath
eter
for t
he fi
rst 2
4 ho
urs,
and
dup
lex
scan
ning
at d
ays
3 an
d 10
.
Ther
e w
as n
o di
ffere
nce
in d
emog
raph
ics
betw
een
grou
ps. T
he p
ain
sore
s at
rest
and
with
RO
M w
ere
sign
ifica
ntly
less
in th
e ep
idur
al g
roup
. RO
M w
as
bette
r in
the
epid
ural
gro
up c
ompa
red
with
the
spin
al
grou
p af
ter d
ay 1.
No
DVT
was
det
ecte
d on
day
3 o
r 10
in e
ither
gro
up. N
o pa
tient
in e
ither
gro
up re
quire
d re
inse
rtio
n of
bla
dder
cat
hete
r for
urin
ary
rete
ntio
n.
By u
sing
epi
dura
l ana
lges
ia in
the
first
7
days
pos
tope
rativ
ely,
we
achi
eved
im
prov
ed e
arly
reha
bilit
atio
n du
e to
ex
celle
nt p
ain
relie
f effe
ct a
nd a
n an
tithr
ombo
tic e
ffect
with
an
effic
acy
com
para
ble
to lo
w m
olec
ular
-wei
ght
hepa
rin.
Pham
Dan
g et
al,
2005
[26]
28 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
wer
e al
loca
ted
rand
omly
to re
ceiv
e a
cont
inuo
us fe
mor
al n
erve
blo
ck o
r con
tinuo
us
bloc
ks o
f bot
h th
e fe
mor
al a
nd s
ciat
ic n
erve
s.
Stim
ulat
ing
cath
eter
s w
ere
used
in a
ll ca
ses.
A
load
ing
dose
of 1
5 m
l rop
ivaca
ine
0.75
%
was
inje
cted
into
eac
h ca
thet
er, f
ollo
wed
by
adm
inis
tratio
n of
ropi
vaca
ine
0.2%
(2–5
ml/h
in
fusi
on v
ia th
e fe
mor
al c
athe
ter;
bolu
s 10
ml
repe
ated
eve
ry 12
hou
rs in
the
scia
tic c
athe
ter).
The
VAS
scor
es a
t res
t wer
e si
gnifi
cant
ly h
ighe
r whe
n th
ere
was
onl
y co
ntin
uous
fem
oral
ner
ve b
lock
than
w
hen
ther
e w
as b
oth
cont
inuo
us fe
mor
al a
nd s
ciat
ic
nerv
e bl
ocks
. Thi
s di
ffere
nce
prog
ress
ivel
y de
crea
sed
and
disa
ppea
red
at 3
6 ho
urs
afte
r sur
gery
. The
co
mbi
ned
fem
oral
and
sci
atic
blo
cks
decr
ease
d th
e m
orph
ine
cons
umpt
ion
by 8
1% a
nd s
igni
fican
tly
decr
ease
d th
e oc
curre
nce
of p
osto
pera
tive
naus
ea
and
vom
iting
.
Dur
ing
the
36 h
ours
imm
edia
tely
af
ter t
otal
kne
e re
plac
emen
t, th
e co
mbi
natio
n of
con
tinuo
us fe
mor
al
and
scia
tic n
erve
blo
cks
impr
oves
an
alge
sia
whi
le d
ecre
asin
g m
orph
ine
cons
umpt
ion
and
post
oper
ativ
e na
usea
an
d vo
miti
ng.
13/2009 pAGE – 12
JointEvidence The multimodal pain management approach in total knee arthroplasty
JointEvidence
K_JE_PainManagement_TKA_08.indd 12 26.3.2009 17:49:52 Uhr
rEFE
rEN
CE
sAM
pLE
TrEA
TMEN
T G
rou
ps A
Nd
pA
iN
MA
NA
GEM
ENT
dET
AiL
sK
Ey r
Esu
LTs
Au
Tho
rs’ C
oN
CLu
sio
Ns
EFFE
CTi
vEN
Ess
oF
TrEA
TMEN
T?*
Fors
ter e
t al,
2005
[27]
72 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Afte
r the
ope
ratio
n, p
atie
nts
rece
ived
an
epid
ural
infu
sion
con
sist
ing
of ro
piva
cain
e
2 m
g m
l(-1)
and
fent
anyl
5 m
icro
g m
l(-1)
eith
er
with
out (
grou
p RF
, n =
33)
or w
ith c
loni
dine
2
mic
rog
ml(-
1) (g
roup
RFC
, n =
36)
. The
in
fusi
on ra
te w
as a
djus
ted
with
in th
e ra
nge
3–7
ml h
(-1).
Aver
age
rate
of i
nfus
ion
was
slig
htly
sm
alle
r in
Gro
up
RFC
than
in g
roup
RF
(mea
n [s
d] 4
.7 [0
.72]
vs
5.2
[0.8
] m
l h[-1
], P
= 0.
004)
. Com
pare
d w
ith th
e RF
gro
up,
patie
nts
in th
e RF
C gr
oup
requ
ired
sign
ifica
ntly
less
re
scue
pai
n m
edic
atio
n, th
at is
i.m
. oxy
codo
ne
(med
ian
[25t
h, 7
5th
perc
entil
e] 0
[0, 7
] vs.
7 [0
, 12]
mg,
P
= 0.
027)
. Arte
rial p
ress
ure
and
hear
t rat
e w
ere
slig
htly
low
er in
gro
up R
FC th
roug
hout
the
stud
y pe
riod
(mea
n di
ffere
nce
betw
een
the
grou
ps
5 m
m H
g [P
<0.
002]
and
3 m
in[-1
] [P
= 0.
12],
resp
ectiv
ely)
. The
gro
ups
did
not d
iffer
sta
tistic
ally
w
ith re
spec
t to
naus
ea, m
otor
blo
ck, a
nd s
edat
ion.
The
smal
l am
ount
of c
loni
dine
add
ed
to th
e lo
w-d
ose
ropi
vaca
ine-
fent
anyl
m
ixtu
re re
duce
d th
e ne
ed fo
r opi
oid
resc
ue p
ain
med
icat
ion
afte
r tot
al
knee
art
hrop
last
y. C
loni
dine
slig
htly
de
crea
sed
arte
rial p
ress
ure
and
hear
t rat
e w
ithou
t jeo
pard
izin
g he
mod
ynam
ics.
Oth
erw
ise,
the
side
ef
fect
pro
files
wer
e co
mpa
rabl
e in
bot
h gr
oups
.
Dav
ies
et a
l, 20
04 [2
8]60
pat
ient
s un
derg
oing
tota
l kn
ee a
rthr
opla
sty
Patie
nts
wer
e pr
ospe
ctiv
ely
rand
omiz
ed to
re
ceiv
e ei
ther
a lu
mba
r epi
dura
l inf
usio
n or
co
mbi
ned
sing
le-s
hot f
emor
al (3
-in-1
) and
sc
iatic
blo
cks
(com
bine
d bl
ocks
). A
ll pa
tient
s re
ceiv
ed s
tand
ard
gene
ral a
nest
hesi
a.
In b
oth
grou
ps, p
ain
on m
ovem
ent w
as w
ell
cont
rolle
d at
dis
char
ge fr
om re
cove
ry a
nd 6
h
post
oper
ativ
ely
but i
ncre
ased
at 2
4 an
d 48
h.
VAS
pain
sco
res
with
the
com
bine
d bl
ocks
wer
e si
gnifi
cant
ly lo
wer
at 2
4 h
(P =
0.0
04).
Tota
l mor
phin
e us
age
was
low
in b
oth
grou
ps: m
edia
n ep
idur
al
grou
p 17
mg
(8–3
2) v
ersu
s co
mbi
ned
bloc
ks 13
mg
(7.
8–27
.5).
Patie
nt s
atis
fact
ion
was
hig
h in
bot
h gr
oups
with
med
ian.
Com
bine
d fe
mor
al (3
-in-1
) and
sci
atic
bl
ocks
offe
r a p
ract
ical
alte
rnat
ive
to
epid
ural
ana
lges
ia fo
r uni
late
ral k
nee
repl
acem
ents
.
Brow
n et
al,
2004
[29]
60 p
atie
nts
unde
rgoi
ng to
tal
knee
art
hrop
last
y
Patie
nts
wer
e ra
ndom
ized
to re
ceiv
e bu
piva
cain
e 20
ml 0
.5%
(100
mg)
or 2
0 m
l no
rmal
sal
ine
inje
cted
into
the
join
t spa
ce
afte
r cap
sule
clo
sure
.
The
bupi
vaca
ine
grou
p ha
d lo
wer
pai
n sc
ores
and
re
duce
d na
rcot
ics
durin
g th
e 24
-hou
r per
iod,
with
a
23-m
inut
e sh
orte
r tim
e to
dis
char
ge fr
om th
e po
st
anes
thes
ia c
are
unit
than
the
plac
ebo
grou
p (P
= .0
2).
Alth
ough
a b
upiva
cain
e bo
lus
inje
cted
at
cap
sule
clo
sure
resu
lts in
dec
reas
ed
pain
leve
ls a
nd n
arco
tic c
onsu
mpt
ion,
it
is n
ot s
tatis
tical
ly s
igni
fican
tly b
ette
r th
an p
lace
bo.
* Sc
ale
of 1
to 5
, whe
re 5
rep
rese
nts
trea
tmen
ts th
at a
ppea
r to
be
very
effe
ctiv
e ba
sed
on th
e re
sults
rep
orte
d, a
nd 1
rep
rese
nts
trea
tmen
ts th
at d
o no
t app
ear
to b
e ef
fect
ive
base
d on
th
e re
sults
rep
orte
d. T
his
ratin
g do
es n
ot ta
ke in
to c
onsi
dera
tion
the
met
hodo
logi
cal r
igor
of e
ach
stud
y.
13/2009 pAGE – 13
JointEvidence The multimodal pain management approach in total knee arthroplasty
JointEvidence
K_JE_PainManagement_TKA_08.indd 13 26.3.2009 17:49:52 Uhr
NoTEsJointEvidence
K_JE_PainManagement_TKA_08.indd 14 26.3.2009 17:49:52 Uhr
NoTEsJointEvidence
K_JE_PainManagement_TKA_08.indd 15 26.3.2009 17:49:52 Uhr
Smith & Nephew Orthopaedics AGKLEOS Global6343 RotkreuzSwitzerland+41 41 798 41 11
[email protected] www.kleos.md
K_JE_PainManagement_TKA_08.indd 16 26.3.2009 17:49:52 Uhr