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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

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13/2009 pAGE – 2JointEvidence


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].

13/2009 pAGE – 3

JointEvidence The multimodal pain management approach in total knee arthroplasty

JointEvidence


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.

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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


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


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


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


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


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


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


NoTEsJointEvidence


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