Nursing dimension

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For this written assignment, select one recent (within the past two years) evidence-based article from a peer reviewed nursing journal that describes a “best practice” in an area of nursing you are interested in. For example, if you would like to be a pediatric nurse, select an article that discusses a best practice in pediatric care.

Cite the article and provide a brief overview of how the results or findings were obtained. Then describe the “best practice.” Conclude your discussion by explaining whether you thought the research findings supported the conclusions and the best practice.

 

Use APA Editorial format and attach a copy of the article.

20 AJN ▼ May 2022 ▼ Vol. 122, No. 5 ajnonline.com

ORIGINAL RESEARCH

A cute pain, characterized as sudden in onset and of limited duration, is one of the most common reasons people seek medical care.1
Acute pain has the potential to interfere with activ-
ities of daily living, and if unrelieved, can progress
to chronic pain. Inadequately managed postoper-
ative pain can worsen patient outcomes and lead
to increased hospital readmissions and health care
costs.1 In 1996, amid numerous reports of inade-
quately managed pain, the American Pain Society
introduced the concept of “pain as the fifth vital
sign,”2 which was soon widely promoted by orga-
nizations such as the Joint Commission3 and the
U.S. Department of Veterans Affairs.4 While an
emphasis on appropriate pain management was
intended to improve patient care, there is some
evidence that this has instead contributed to the
overuse of opioids.5

Opioid pain medications, which are often pre-
scribed for acute pain, work by interacting with
specific opioid receptors in the body and brain.
When taken as prescribed by a physician for a short
period of time, these medications are generally safe.
But because they also induce feelings of euphoria,
there is potential for misuse. As the National Insti-
tute on Drug Abuse has cautioned, their “regular
use—even as prescribed by a doctor—can lead to
dependence and, when misused, . . . to addiction,”
as well as to the abuse of unprescribed opioids such

The evidence supports the use of opioid-sparing strategies in managing
acute pain.

as heroin and synthetic opioids such as fentanyl.6
The likelihood of developing an opioid use disorder
depends on several factors, including the amount of
opioid taken and the length of time the medication
is used for acute pain.7

The misuse of and addiction to opioids has
become a national health crisis of epidemic propor-
tions.7, 8 In 2019, opioids accounted for more than
70% of all drug overdose deaths in the United
States, with accidental opioid overdose claiming
nearly 50,000 lives.9 The economic burden associ-
ated with opioid misuse and addiction—including
health care costs, lost productivity, and crime—has
been estimated at $78.5 billion per year.7

Federal and nonfederal agencies have taken steps
to address the opioid epidemic, including increased
surveillance and tracking of drug overdoses,
improved access to addiction treatment programs,
enhanced prescription drug monitoring programs,
and new prescribing practice guidelines.8, 10-12 Among
the last are guidelines issued by the Enhanced Recov-
ery After Surgery (ERAS) Society (https://erassociety.
org/guidelines), which emphasize the use of multi-
modal analgesia (also called opioid-sparing analgesia).13
(ERAS protocols also include other interventions
such as preoperative counseling, nutritional recom-
mendations, and early postoperative mobilization.14)
Multimodal analgesia involves the simultaneous use of
multiple analgesic agents, nonopioid and opioid, that

Combating the Opioid
Epidemic Through Nurse
Use of Multimodal
Analgesia: An Integrative
Literature Review

[email protected] AJN ▼ May 2022 ▼ Vol. 122, No. 5 21

ABSTRACT
Background: Opioid misuse and addiction have become a national crisis. New pain management guide-
lines call for the use of multimodal analgesia to manage acute pain. In hospital settings, a clinical decision
aid that emphasizes multimodal analgesia may improve nurses’ use of this opioid-sparing strategy.

Purpose: This integrative review was conducted to provide nurses with evidence-based information on
the opioid-sparing benefits of multimodal analgesia.

Methods: A literature search was conducted using several electronic databases and Google Scholar.
These initial searches yielded 136 articles of interest. Twenty-eight were selected for retrieval and in-depth
appraisal; of these, 13 met all inclusion criteria.

Results: Of the 13 reviewed studies, six were randomized controlled trials, six were retrospective cohort
or population-based studies, and one was a qualitative study. Overall, the findings provided strong evi-
dence that multimodal analgesia is effective in managing acute pain in surgical patients while reducing
opioid requirements. Several studies also found that multimodal analgesia was associated with shorter
hospital lengths of stay.

Conclusions: With the appropriate tools and education, nurses can make the transition from traditional
opioids to multimodal analgesia strategies. In so doing, they can have a significant positive impact on the
opioid epidemic. Hospital leaders must address nursing practice regarding the use of opioids alone versus
multimodal analgesia for the management of acute pain. Clinical decision tools such as the Michigan Opi-
oid Safety Score may help nurses adopt new acute pain management guidelines. Further research regard-
ing nursing practice and the opioid epidemic is needed.

Keywords: clinical decision tools, multimodal analgesia, opioid epidemic, opioids, pain, pain manage-
ment, surgical patients

act synergistically to reduce pain and minimize the
risk of opioid-related side effects.13 (See Multimodal
Analgesia and the Pain Pathway.15) In hospitalized
patients, the use of multimodal analgesia has been
further shown to reduce the risk of opioid-related
adverse events, decrease hospital lengths of stay, and
reduce opioid misuse and abuse after discharge.16

Yet despite compelling evidence demonstrating
the benefits of multimodal analgesia for pain man-
agement in the acute care setting and newer guide-
lines directing prescribers to adopt an opioid-sparing
strategy, nursing practice has largely not reflected
this. Bedside nurses often practice autonomously in
managing patients’ acute pain, selecting an analgesic
from a list of ordered medications and basing this
selection on a patient’s stated numeric pain score.
Yet this practice has been associated with increased
opioid-induced adverse effects.17 In a chaotic and
demanding practice environment, it can be a chal-
lenge to assess a patient’s pain and risk with regard
to sedation and intervene in a way that promotes
comfort while maintaining safety. Furthermore, the
availability of previously used pain management
order sets, as well as the expectation that patients
should be relatively pain free, continue to influence
nursing practice toward an overreliance on opioids.

Purpose. The aim of this review was to present
evidence on the benefits of multimodal analgesia in
reducing opioid use for pain management in the
acute care setting.

METHODS
Literature search. The integrative review method
recommended by Whittemore and Knafl18 was used
to search, analyze, and synthesize the literature rele-
vant to the topic of interest. An initial search was
conducted for peer-reviewed articles through the
following databases: Academic Search Complete,
CINAHL, Cochrane Library, Health Policy Refer-
ence Center, MEDLINE, Nursing & Allied Health,
ProQuest Central, and ScienceDirect. The following
search terms were used in various combinations:
multimodal analgesia, reduced opioid use, hospitalized
patient, cardiac surgery, orthopedic surgery, spine sur-
gery, and study. The search was limited to articles
published in English between January 1, 2015, and
July 31, 2020. Citations of randomized controlled
trials, clinical practice guidelines, expert opinion,
and primary qualitative and quantitative studies
were carefully scanned for relevance to the topic of
interest. The original search yielded 131 articles.

Another search was conducted via Google Scholar
for seven articles of interest referenced by authors of
articles obtained in the initial search. This second
search was conducted using the authors’ names; pub-
lication dates and language limits were not applied
this time. Of the seven articles, five were selected as
relevant, resulting in a total of 136 articles.

Inclusion and exclusion criteria. Inclusion was
limited to articles reporting on studies that examined
the effects of multimodal analgesia in patients over

By Jennifer René Tavernier, DNP, RN, CCM

22 AJN ▼ May 2022 ▼ Vol. 122, No. 5 ajnonline.com

the age of 18 years and were available in full text
and published in English in peer-reviewed journals.
More specifically, studies evaluating multimodal
analgesia strategies that involved medications likely
to be administered by bedside nurses on a medical–
surgical unit were eligible for inclusion. Studies
involving childbirth or dental surgeries were excluded,
as were those evaluating multimodal analgesia strat-
egies involving epidural analgesia, nerve blocks, or
inhaled medications (unless they also evaluated the
postoperative addition of nonopioid analgesics).
Also excluded were studies investigating pain man-
agement for patients with cancer and patients in
treatment for or with histories of opioid addiction,
because of the unique pain management strategies
required. Lastly, studies comparing the efficacy of
different modes of analgesic delivery were excluded.

Twenty-eight articles were selected for in-depth
appraisal; of these, three could not be retrieved.
Regarding multimodal analgesia, the primary out-
come of interest was the opioid-sparing effects of
this strategy. Three secondary outcomes of interest
emerged during the in-depth appraisal: the effects
of multimodal analgesia on pain scores, hospital
lengths of stay, and nurses’ feelings regarding acute
pain management and the opioid epidemic. Stud-
ies showing outcomes related to anything other
than these four were excluded, leaving 18 arti-
cles. Another five articles were excluded in a final
appraisal round because the surgical procedures
(laparoscopic cholecystectomy, laparoscopic pros-
tatectomy) were performed in outpatient settings
and were likely to result in less pain than is gener-
ally experienced by postsurgical inpatients. Thirteen
articles met all the inclusion criteria for this integra-

tive review. See Figure 1 for a flowchart of the liter-
ature selection process.

Multimodal strategies for pain management
include a variety of pharmacologic and nonpharma-
cologic interventions. This review focused on stud-
ies examining the effects of nonopioid agents used
either as primary medication or as adjuncts to opi-
oid medications. The specific medications used in
these studies varied; and in a few studies, more than
one nonopioid adjunct was used. While it may be
important to understand the efficacy of individual
medications used in a particular multimodal analgesia
regimen, this review considered the opioid-sparing
effects of any multimodal analgesia strategy.

The quality and strength of eligible studies,
reviews, and guidelines were evaluated using the
Johns Hopkins Evidence Level and Quality Guide
(www.hopkinsmedicine.org/evidence-based-practice/_
docs/appendix_c_evidence_level_quality_guide.pdf).

RESULTS
Study characteristics. Of the 13 studies included in
this review, six were randomized controlled trials,19-24
six were retrospective cohort or population-based
studies25-30 (including one retrospective cross-sectional
cohort study29), and one was a qualitative study.31

Peri- and postoperative multimodal analgesia
strategies investigated in the 12 quantitative studies
included
• oral or iv acetaminophen (also known as

paracetamol outside the United States).25, 27
• tramadol and paracetamol, given by mouth.19

• iv ibuprofen.21

• iv ibuprofen and iv acetaminophen.20, 23, 28

• one or more of these: acetaminophen, steroids,
gabapentinoids, ketamine, nonsteroidal antiin-
flammatory drugs (NSAIDs), cyclooxygenase 2
(COX-2) inhibitors, peripheral nerve blocks.26, 29

• celecoxib, pregabalin, and extended-release oxy-
codone.22

• dexamethasone, gabapentin, ibuprofen, and
paracetamol.24

• ketamine, ketorolac, and acetaminophen (as
part of an ERAS protocol).30

The six randomized controlled trials provided the
highest level of evidence and support for multimodal
analgesia use. The study by Daniels and colleagues
among 276 patients undergoing bunionectomy
reported consistent results that are generalizable to
others undergoing this surgery.20 The study by Gago
Martínez and colleagues among 135 patients under-
going abdominal surgeries also reported consistent
results; and because this was a multisite study, the
findings are more likely to be generalizable to others
undergoing such surgeries.21 The study by Rafiq and
colleagues had a robust sample size of 151 patients
undergoing cardiac surgeries,24 although its open-
label design carries a higher risk of bias. (In open-

Multimodal Analgesia and the Pain
Pathway

Inadequately managed pain is harmful under
any circumstances; in light of the ongoing
opioid epidemic, researchers have been explor-
ing ways to impact the pain pathway and alle-
viate pain using opioid-sparing strategies. The
pain pathway comprises four processes: trans-
duction (the conversion of a stimulus into sig-
nals at nerve endings), transmission (the relay-
ing of signals from points of origin to the brain),
modulation (neural regulation of pain signal-
ing), and percep tion (subjective awareness of
pain). Pain management involves influencing
one or more of these processes. Multimodal
analgesia targets all four, doing so by combin-
ing individually tailored doses of nonopioid
drugs, each with different mechanisms of
action, along with smaller doses of opioids.15

[email protected] AJN ▼ May 2022 ▼ Vol. 122, No. 5 23

label studies, both the providers and the patients
know the drug or treatment given.) The studies by
Garcia and colleagues,22 Gupta and colleagues,23 and
Altun and colleagues19 were each conducted at a sin-
gle acute care site and had relatively small sample
sizes of 22, 74, and 50 patients, respectively. Though
these factors limit the generalizability of the findings,
these studies demonstrated consistent results.

The six retrospective cohort or population-
based studies also provided relatively good support
for multimodal analgesia use, although retrospec-
tive studies offer a lower level of evidence and can-
not establish causation. Cozowicz and colleagues,26
Maiese and colleagues,28 and Memtsoudis and col-
leagues29 each conducted large-scale retrospective
cohort reviews from large databases representing a
multitude of U.S. hospitals. Patients in these stud-
ies underwent orthopedic surgeries. Orthopedic
procedures are known to be among the most com-
plex and painful procedures, and this specialty was
among the first to investigate the use of multimodal
analgesia.32 Three smaller-scale retrospective stud-
ies contributed further useful findings. Bollinger and
colleagues25 and Girardot and colleagues27 each con-
ducted retrospective studies among patients under-
going orthopedic procedures. Warren and colleagues
conducted a retrospective review of patients under-
going open ventral hernia repair.30

Lastly, Angelini and colleagues conducted a quali-
tative study exploring how nurses and other health
care providers feel about managing acute pain in
patients undergoing planned lumbar spine surgery.31
Although qualitative studies provide a lower level of
evidence and are subject to increased risk of bias,
they can provide a deeper understanding of the com-
plex experiences of providers.

Quantitative analytics were used to calculate
mean values for demographic data when adequate
data were provided. Of the 13 studies, nine were
conducted either in U.S. hospitals (randomized con-
trolled trials)20, 22, 23 or using U.S. hospital databases
(retrospective cohort or population-based stud-
ies).25-30 Three randomized controlled trials took
place outside the United States, including single-site
trials conducted in Denmark24 and in Turkey19 and a
multisite trial conducted at nine hospitals in Spain.21
The qualitative study was conducted at a single hos-
pital in Sweden.31 For the 12 quantitative studies,
the mean or median age of participants ranged from
42.4 to 83.6 years. In the nine studies reporting par-
ticipants’ sex, 56% of the participants were women
and 44% were men. For detailed information on
the 13 reviewed studies, see Table 1.

Findings. Though the 13 reviewed studies varied
in the medications used, each demonstrated the effi-
cacy and safety of multimodal analgesia in reducing
opioid requirements among surgical patients. (One
of these studies evaluated use of an ERAS protocol,

which included multimodal analgesia.30) In several
of these studies, shorter hospitalizations were also
reported.25, 26, 28-30

Reduced opioid requirements. The use of acet-
aminophen, whether given orally or intravenously,
was shown to decrease opioid use in both orthope-
dic and cardiac surgeries. In a prospective, double-
blind clinical study among 50 patients undergoing
elective coronary artery bypass grafting, Altun and
colleagues found that patient-controlled iv morphine
requirements dropped by 50% in patients given a
combination of oral paracetamol and tramadol
(a synthetic opioid).19 In a retrospective comparative
cohort study of 332 patients who had undergone
surgery for hip fracture, Bollinger and colleagues

Figure 1. PRISMA Flow Diagram of Studies

Id
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(n = 131)

and Google Scholar
(n = 7)

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sought for retrieval
(n = 28)

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(n = 13)

Full-text articles excluded
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•   Outcomes not related to

effects of multimodal
analgesia

•   Study sample demograph-
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(n = 2)

Records excluded
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•   Study involved childbirth

or dental surgeries
•   Study evaluated epidural

analgesia, nerve blocks, or
inhaled medication)a

•   Subjects had cancer or were
in treatment for or had his-
tories of opioid addiction

•   Study evaluated efficacy
of different modes of anal-
gesic delivery

•   Article not in English

PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
a The study remained under consideration if it also evaluated the postoperative addition
of nonopioids.

24 AJN ▼ May 2022 ▼ Vol. 122, No. 5 ajnonline.com

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as
si

st
an

ts
)

w
o

u
ld

h
av

e
ad

d
ed

va

lu
ab

le
in

fo
rm

a-
ti

o
n

.

B
o

lli
n

g
er

A
J,

et

a
l.

20
15

25

R
et

ro
sp

ec
ti

ve
c

o
m

p
ar


at

iv
e

co
h

o
rt

s
tu

d
y

Le
ve

l I
II

33
2

g
er

ia
tr

ic
p

at
ie

n
ts

w
it

h

33
6

h
ip

fr
ac

tu
re

s

M
ea

n
a

g
e:

8
1.

8–
83

.3
y

ea
rs

Le
ve

l 1
tr

au
m

a
ce

n
te

r;

U
n

it
ed

S
ta

te
s

O
bj

ec
tiv

es
: T

o
e

va
lu

at
e

th
e

ef
fe

ct
o

f s
ch

ed
u

le
d

iv
a

ce
ta

m
in

o
p

h
en

fo
r p

er
i-

o
p

er
at

iv
e

p
ai

n
m

an
ag

em
en

t o
n

h
o

sp
it

al
L

O
S,

p
ai

n
le

ve
ls

, n
ar

co
ti

c
u

se
,

ra
te

o
f m

is
se

d
p

h
ys

ic
al

th
er

ap
y

se
ss

io
n

s,
a

d
ve

rs
e

ef
fe

ct
s,

a
n

d
d

is
ch

ar
g

e
d

is
p

o
si

ti
o

n
.

Re
su

lts
: T

h
e

tr
ea

tm
en

t g
ro

u
p

h
ad

a
s

ta
ti

st
ic

al
ly

s
ig

n
ifi

ca
n

tl
y

sh
o

rt
er

m
ea

n

h
o

sp
it

al
L

O
S,

lo
w

er
m

ea
n

p
ai

n
s

co
re

, l
o

w
er

m
ea

n
n

ar
co

ti
c

u
se

, l
o

w
er

ra
te

o

f m
is

se
d

p
h

ys
ic

al
th

er
ap

y
se

ss
io

n
s,

a
n

d
h

ig
h

er
li

ke
lih

o
o

d
o

f d
is

ch
ar

g
e

to
h

o
m

e.

C
on

cl
us

io
ns

: T
re

at
m

en
t w

it
h

iv
a

ce
ta

m
in

o
p

h
en

im
p

ro
ve

d
p

ai
n

, d
ec

re
as

ed

h
o

sp
it

al
L

O
S,

im
p

ro
ve

d
a

ct
iv

it
y,

a
n

d
w

as
m

o
re

li
ke

ly
to

le
ad

to
d

is
ch

ar
g

e
to

h
o

m
e.

R
et

ro
sp

ec
ti

ve

co
h

o
rt

s
tu

d
ie

s
ca

n

n
o

t s
h

o
w

c
au

sa

ti
o

n
, o

n
ly

a
ss

o
ci

a-
ti

o
n

.

[email protected] AJN ▼ May 2022 ▼ Vol. 122, No. 5 25

C
o

zo
w

ic
z

C
,

et
a

l.
20

20
26

R
et

ro
sp

ec
ti

ve
p

o
p

u
la


ti

o
n

-b
as

ed
c

o
h

o
rt

st

u
d

y

Le
ve

l I
II

26
5,

53
8

p
at

ie
n

ts
re

ce
iv

in
g

lu

m
b

ar
s

p
in

e
fu

si
o

n
s

u
r-

g
er

y

M
ed

ia
n

a
g

e:
6

0–
62

y
ea

rs

Fe
m

al
e:

1
50

,9
22

M
al

e:
1

14
,6

16

Pr
em

ie
r H

ea
lt

h
ca

re
d

at
a-

b
as

e
o

f 4
47

h
o

sp
it

al
s;

U

n
it

ed
S

ta
te

s

O
bj

ec
tiv

es
: T

o
e

va
lu

at
e

th
e

ef
fe

ct
s

o
f M

M
A

o
n

p
at

ie
n

ts
u

n
d

er
g

o
in

g
lu

m

b
ar

s
p

in
e

fu
si

o
n

s
u

rg
er

y.

Re
su

lts
: O

p
io

id
-o

n
ly

a
n

al
g

es
ia

w
as

c
o

m
p

ar
ed

w
it

h
M

M
A

(w
h

ic
h

m
ig

h
t

in
cl

u
d

e
sy

st
em

ic
o

p
io

id
p

lu
s

ac
et

am
in

o
p

h
en

, s
te

ro
id

s,
g

ab
ap

en
ti

n
o

id
s,

ke

ta
m

in
e,

N
SA

ID
s,

C
O

X
-2

in
h

ib
it

o
rs

, o
r n

eu
ra

xi
al

a
n

es
th

es
ia

).
In

g
en

er
al

,
th

er
e

w
er

e
n

o
s

ig
n

ifi
ca

n
t d

iff
er

en
ce

s
in

o
p

io
id

p
re

sc
ri

p
ti

o
n

s.
B

u
t i

n
h

o
sp

i-
ta

ls
th

at
ro

u
ti

n
el

y
u

se
d

C
O

X
-2

in
h

ib
it

o
rs

a
n

d
N

SA
ID

s,
th

er
e

w
er

e
d

ec
re

as
es

in
o

p
io

id
p

re
sc

ri
p

ti
o

n
s

an
d

h
o

sp
it

al
L

O
S.

C
on

cl
us

io
ns

: T
h

e
u

se
o

f N
SA

ID
s

an
d

C
O

X
-2

in
h

ib
it

o
rs

w
as

a
ss

o
ci

at
ed

w
it

h

re
d

u
ce

d
o

p
io

id
re

q
u

ir
em

en
ts

a
n

d
s

h
o

rt
er

h
o

sp
it

al
iz

at
io

n
s.

R
et

ro
sp

ec
ti

ve

co
h

o
rt

s
tu

d
ie

s
ca

n
n

o
t s

h
o

w

ca
u

sa
ti

o
n

, o
n

ly

as
so

ci
at

io
n

.

D
an

ie
ls

S
E,

et

a
l.

20
19

20

M
u

lt
is

it
e,

p
ro

sp
ec

ti
ve

,
ra

n
d

o
m

iz
ed

, d
o

u
b

le

b
lin

d
, p

la
ce

b
o


co

n
tr

o
lle

d
, f

ac
to

ri
al

cl
in

ic
al

tr
ia

l

Le
ve

l I

27
6

p
at

ie
n

ts
u

n
d

er
g

o
in

g

b
u

n
io

n
ec

to
m

y

M
ea

n
a

g
e:

4
2.

4
ye

ar
s

Fe
m

al
e:

2
25

M
al

e:
5

1

2
cl

in
ic

al
re

se
ar

ch
h

o
sp

i-
ta

ls
; U

n
it

ed
S

ta
te

s

O
bj

ec
tiv

es
: T

o
in

ve
st

ig
at

e
th

e
ef

fic
ac

y
an

d
s

af
et

y
o

f a
n

iv
fi

xe
d

d
o

se
o

f
co

m
b

in
ed

ib
u

p
ro

fe
n

a
n

d
a

ce
ta

m
in

o
p

h
en

a
ft

er
b

u
n

io
n

ec
to

m
y.

Re
su

lts
: T

h
e

im
p

ac
t o

f t
re

at
m

en
t o

n
p

ai
n

in
te

n
si

ty
d

iff
er

en
ce

s
fr

o
m

b
as

e-
lin

e
o

ve
r 4

8
h

o
u

rs
w

as
s

ig
n

ifi
ca

n
tl

y
g

re
at

er
in

th
e

g
ro

u
p

re
ce

iv
in

g
th

e
fix

ed
d

o
se

, c
o

m
p

ar
ed

w
it

h
o

th
er

g
ro

u
p

s
re

ce
iv

in
g

ib
u

p
ro

fe
n

, a
ce

ta
m

in
o


p

h
en

, o
r p

la
ce

b
o.

T
h

e
fix

ed
-d

o
se

g
ro

u
p

a
ls

o
s

h
o

w
ed

s
ig

n
ifi

ca
n

tl
y

re
d

u
ce

d
o

p
io

id
re

q
u

ir
em

en
ts

.

C
on

cl
us

io
ns

: A
n

iv
fi

xe
d

d
o

se
c

o
m

b
in

in
g

ib
u

p
ro

fe
n

a
n

d
a

ce
ta

m
in

o
p

h
en

p

ro
vi

d
es

b
et

te
r p

ai
n

re
lie

f a
n

d
re

d
u

ce
d

o
p

io
id

u
se

th
an

th
e

u
se

o
f i

b
u


p

ro
fe

n
, a

ce
ta

m
in

o
p

h
en

, o
r p

la
ce

b
o

a
lo

n
e.

Th
e

re
su

lt
s

ar
e

g
en

er
al

iz
ab

le
to

“t

yp
ic

al
” p

at
ie

n
ts

u

n
d

er
g

o
in

g
b

u
n


io

n
ec

to
m

y
b

u
t

m
ay

n
o

t b
e

g
en

er

al
iz

ab
le

to
s

o
m

e.

G
ag

o

M
ar


n

ez
A

,
et

a
l.

20
16

21

M
u

lt
is

it
e,

ra
n

d
o

m
iz

ed
, d

o
u

b
le


b

lin
d

, p
la

ce
b

o

co
n

tr
o

lle
d

tr
ia

l

Le
ve

l I

20
6

p
at

ie
n

ts
(4

7
o

rt
h

o
p

e-
d

ic
s

u
rg

er
y,

1
59

a
b

d
o

m
i-

n
al

s
u

rg
er

y)

M
ea

n
a

g
e:

5
1.

93
–5

3.
49

ye

ar
s

9
h

o
sp

it
al

s;
S

p
ai

n

O
bj

ec
tiv

es
: T

o
e

va
lu

at
e

th
e

ef
fic

ac
y

an
d

s
af

et
y

o
f i

v
ib

u
p

ro
fe

n
o

n
p

o
st

o
p


er

at
iv

e
p

ai
n

a
ft

er
o

rt
h

o
p

ed
ic

o
r a

b
d

o
m

in
al

s
u

rg
er

y.

Re
su

lts
: M

o
rp

h
in

e
re

q
u

ir
em

en
ts

w
er

e
si

g
n

ifi
ca

n
tl

y
re

d
u

ce
d

, a
n

d
p

at
ie

n
ts

h

ad
d

ec
re

as
ed

p
ai

n
a

t r
es

t.

C
on

cl
us

io
ns

: i
v
ib

u
p

ro
fe

n
s

ig
n

ifi
ca

n
tl

y
re

d
u

ce
d

p
o

st
o

p
er

at
iv

e
m

o
rp

h
in

e
re

q
u

ir
em

en
ts

.

Th
e

st
u

d
y

w
as

co

n
d

u
ct

ed
in

Sp

ai
n

, w
h

er
e

d

iff
er

en
t p

ro
to

co
ls

an

d
m

ed
ic

at
io

n
s

m
ay

b
e

u
se

d
.

G
ar

ci
a

R
M

,
et

a
l.

20
13

22

Pr
o

sp
ec

ti
ve

, r
an

d
o

m

iz
ed

c
o

n
tr

o
lle

d
tr

ia
l

Le
ve

l I

22
p

at
ie

n
ts

w
h

o
u

n
d

er

w
en

t p
ri

m
ar

y
m

u
lt

ile
ve

l
lu

m
b

ar
d

ec
o

m
p

re
ss

io
n

M
ea

n
a

g
e:

5
8.

2–
68

.6
y

ea
rs

H
o

sp
it

al
; U

n
it

ed
S

ta
te

s

O
bj

ec
tiv

es
: T

o
e

va
lu

at
e

th
e

ef
fic

ac
y

o
f a

n
o

ve
l M

M
A

re
g

im
en

(p
re

g
ab

al
in

an

d
o

xy
co

n
ti

n
) i

n
re

d
u

ci
n

g
p

o
st

o
p

er
at

iv
e

p
ai

n
le

ve
ls

a
n

d
iv

m
o

rp
h

in
e

re
q

u
ir

em
en

ts
a

ft
er

lu
m

b
ar

d
ec

o
m

p
re

ss
io

n
s

u
rg

er
y.

Re
su

lts
: T

h
e

av
er

ag
e

o
ve

ra
ll

m
o

rp
h

in
e

re
q

u
ir

em
en

t w
as

5
8%

lo
w

er
in

th
e

tr
ea

tm
en

t g
ro

u
p

th
an

in
th

e
co

n
tr

o
l g

ro
u

p
.

C
on

cl
us

io
ns

: A
d

m
in

is
te

ri
n

g
a

c
o

m
b

in
at

io
n

o
f o

p
io

id
s

an
d

n
o

n
o

p
io

id
s

si
g


n

ifi
ca

n
tl

y
re

d
u

ce
d

p
o

st
o

p
er

at
iv

e
m

o
rp

h
in

e
re

q
u

ir
em

en
ts

.

Th
e

st
u

d
y’

s
sm

al
l

sa
m

p
le

s
iz

e
an

d

si
n

g
le

-s
it

e
se

tt
in

g

lim
it

g
en

er
al

iz
ab

il-
it

y
o

f f
in

d
in

g
s.

26 AJN ▼ May 2022 ▼ Vol. 122, No. 5 ajnonline.com

G
ir

ar
d

o
t K

,
et

a
l.

20
20

27

B
ef

o
re

-a
n

d
-a

ft
er

co

h
o

rt
s

tu
d

y

Le
ve

l I

24
8

p
at

ie
n

ts
w

it
h

h
ip

fr

ac
tu

re
s

M
ea

n
a

g
e:

8
3.

5–
83

.6
y

ea
rs

Fe
m

al
e:

1
84

M
al

e:
6

4

H
o

sp
it

al
; U

n
it

ed
S

ta
te

s

O
bj

ec
tiv

es
: T

o
e

va
lu

at
e

w
h

et
h

er
th

e
u

se
o

f a
s

ta
n

d
ar

d
iz

ed
M

M
A

o
rd

er
s

et

(s
ch

ed
u

le
d

p
re

– a
n

d
p

o
st

o
p

er
at

iv
e

o
ra

l o
r i

v
a

ce
ta

m
in

o
p

h
en

) c
o

u
ld

d

ec
re

as
e

o
p

io
id

u
se

w
it

h
o

u
t i

n
cr

ea
si

n
g

p
ai

n
s

co
re

s
in

g
er

ia
tr

ic
p

at
ie

n
ts

u

n
d

er
g

o
in

g
h

ip
fr

ac
tu

re
s

u
rg

er
y.

O
p

io
id

u
se

w
as

m
ea

su
re

d
in

O
M

Es
.

Re
su

lts
: C

o
m

p
ar

ed
w

it
h

th
e

p
re

o
rd

er
s

et
g

ro
u

p
, t

o
ta

l a
n

d
p

o
st

o
p

er
at

iv
e

O
M

Es
w

er
e

re
d

u
ce

d
in

th
e

p
o

st
o

rd
er

s
et

g
ro

u
p

(b
y

22
.6

%
a

n
d

5
3.

6%
,

re
sp

ec
ti

ve
ly

).

C
on

cl
us

io
ns

: T
h

e
st

an
d

ar
d

iz
ed

M
M

A
o

rd
er

s
et

re
d

u
ce

d
p

o
st

o
p

er
at

iv
e

an
d

to

ta
l o

p
io

id
re

q
u

ir
em

en
ts

.

Th
e

st
u

d
y

w
as

co

n
d

u
ct

ed
a

t a

si
n

g
le

s
it

e,
w

h
ic

h

lim
it

s
g

en
er

al
iz

ab
il-

it
y

o
f f

in
d

in
g

s.

G
u

p
ta

A
,

et
a

l.
20

16
23

R
an

d
o

m
iz

ed
c

o
n


tr

o
lle

d
tr

ia
l

Le
ve

l I

74
e

le
ct

iv
e

kn
ee

o
r h

ip

ar
th

ro
p

la
st

y
p

at
ie

n
ts

M
ea

n
a

g
e:

5
7.

8–
58

.3
y

ea
rs

Fe
m

al
e:

4
6

M

al
e:

2
8

Te
rt

ia
ry

h
o

sp
it

al
;

U
n

it
ed

S
ta

te
s

O
bj

ec
tiv

es
: T

o
e

va
lu

at
e

th
e

sa
fe

ty
a

n
d

e
ff

ic
ac

y
o

f p
er

io
p

er
at

iv
e

ad
m

in
is


tr

at
io

n
o

f i
v
ib

u
p

ro
fe

n
a

lo
n

e
an

d
in

c
o

m
b

in
at

io
n

w
it

h
iv

a
ce

ta
m

in
o

p
h

en

in
p

at
ie

n
ts

u
n

d
er

g
o

in
g

to
ta

l k
n

ee
o

r h
ip

s
u

rg
er

y.

Re
su

lts
: i

v
a

ce
ta

m
in

o
p

h
en

a
n

d
ib

u
p

ro
fe

n
re

su
lt

ed
in

s
ig

n
ifi

ca
n

tl
y

lo
w

er

p
ai

n
s

co
re

s
o

n
d

ay
3

o
n

ly
. O

p
io

id
re

q
u

ir
em

en
ts

a
n

d
a

d
ve

rs
e

ev
en

ts
w

er
e

si
g

n
ifi

ca
n

tl
y

le
ss

in
p

at
ie

n
ts

re
ce

iv
in

g
b

o
th

iv
a

ce
ta

m
in

o
p

h
en

a
n

d
iv

ib
u


p

ro
fe

n
. D

iff
er

en
ce

s
in

h
o

sp
it

al
L

O
S

w
er

e
n

o
t s

ta
ti

st
ic

al
ly

s
ig

n
ifi

ca
n

t.

C
on

cl
us

io
ns

: C
o

m
p

ar
ed

w
it

h
iv

ib
u

p
ro

fe
n

a
lo

n
e,

th
e

co
m

b
in

at
io

n
o

f i
v
ib

u

p
ro

fe
n

a
n

d
iv

a
ce

ta
m

in
o

p
h

en
re

su
lt

ed
in

s
o

m
e

lo
w

er
in

g
o

f p
ai

n
s

co
re

s,

w
it

h
fe

w
er

o
p

io
id

-r
el

at
ed

a
d

ve
rs

e
ev

en
ts

a
n

d
re

d
u

ce
d

n
ee

d
fo

r o
p

io
id

s.

Th
e

st
u

d
y’

s
sm

al
l

sa
m

p
le

s
iz

e
an

d

si
n

g
le

-s
it

e
se

tt
in

g

lim
it

g
en

er
al

iz
ab

il-
it

y
o

f f
in

d
in

g
s.

It
s

u
se

o
f a

c
o

n
ve


n

ie
n

ce
s

am
p

le

in
cr

ea
se

s
lik

el
i-

h
o

o
d

o
f b

ia
s.

M
ai

es
e

B
A

,
et

a
l.

20
17

28

R
et

ro
sp

ec
ti

ve
o

b
se

r-
va

ti
o

n
al

a
n

al
ys

is

Le
ve

l I
II

14
4,

25
4

p
at

ie
n

ts
w

it
h

to
ta

l
h

ip
o

r t
o

ta
l k

n
ee

a
rt

h
ro


p

la
st

y,
o

r s
u

rg
ic

al
h

ip
fr

ac

tu
re

re
p

ai
r

M
ea

n
a

g
e:

6
1.

4–
62

.1
y

ea
rs

Tr
u

ve
n

M
ar

ke
tS

ca
n

H
o

sp
i-

ta
l D

ru
g

D
at

ab
as

e
o

f 6
00

h

o
sp

it
al

s;
U

n
it

ed
S

ta
te

s

O
bj

ec
tiv

es
: T

o
e

va
lu

at
e

th
e

im
p

ac
t o

n
h

o
sp

it
al

iz
at

io
n

c
o

st
s

o
f u

si
n

g
M

M
A

(iv

a
ce

ta
m

in
o

p
h

en
a

n
d

a
n

o
th

er
n

o
n

o
p

io
id

) v
er

su
s

iv
o

p
io

id
s

al
o

n
e

fo
r

p
o

st
o

p
er

at
iv

e
p

ai
n

m
an

ag
em

en
t.

Re
su

lts
: M

ea
n

(S
D

) v
al

u
es

fo
r t

o
ta

l h
o

sp
it

al
iz

at
io

n
c

o
st

s
w

er
e

si
g

n
ifi

ca
n

tl
y

lo
w

er
in

th
e

M
M

A
g

ro
u

p
($

12
,5

40
[$

9,
56

4]
) t

h
an

th
e

g
ro

u
p

re
ce

iv
in

g
o

p
i-

o
id

s
al

o
n

e
($

13
,2

42
[$

35
,8

25
])

.

C
on

cl
us

io
ns

: T
h

e
u

se
o

f i
v
a

ce
ta

m
in

o
p

h
en

s
ig

n
ifi

ca
n

tl
y

re
d

u
ce

d
h

o
sp

it
al

co

st
s

fo
r p

at
ie

n
ts

u
n

d
er

g
o

in
g

o
rt

h
o

p
ed

ic
s

u
rg

er
ie

s.

R
et

ro
sp

ec
ti

ve

co
h

o
rt

s
tu

d
ie

s

ca
n

n
o

t s
h

o
w

ca

u
sa

ti
o

n
, o

n
ly

as

so
ci

at
io

n
.

M
em

ts
o

u
d

is

SG
, e

t a
l.

20
18

29

R
et

ro
sp

ec
ti

ve
,

p
o

p
u

la
ti

o
n

-b
as

ed
,

cr
o

ss
-s

ec
ti

o
n

al
c

o
h

o
rt

st

u
d

y

Le
ve

l I
II

To
ta

l h
ip

s
u

rg
er

ie
s:

51

2,
39

3

To
ta

l k
n

ee
a

rt
h

ro
p

la
st

ie
s:

1,

02
8,

06
9

O
bj

ec
tiv

es
: T

o
p

ro
vi

d
e

la
rg

e
-s

ca
le

d
at

a
re

g
ar

d
in

g
th

e
n

u
m

b
er

o
f a

n
d

t
yp

e
o

f a
n

al
g

es
ic

s
(o

p
io

id
s

p
lu

s
at

le
as

t o
n

e
o

f t
h

es
e:

p
er

ip
h

er
al

n
er

ve
b

lo
ck

s,

ac
et

am
in

o
p

h
en

, s
te

ro
id

s,
g

ab
ap

en
ti

n
o

id
s,

N
SA

ID
s,

C
O

X
-2

in
h

ib
it

o
rs

, k
et


am

in
e)

a
ss

o
ci

at
ed

w
it

h
re

d
u

ce
d

o
p

io
id

p
re

sc
ri

p
ti

o
n

s,
c

o
m

p
lic

at
io

n
s,

a
n

d

re
so

u
rc

e
u

ti
liz

at
io

n
.

R
et

ro
sp

ec
ti

ve

st
u

d
ie

s
ca

n
n

o
t

sh
o

w
c

au
sa

ti
o

n
,

o
n

ly
a

ss
o

ci
at

io
n

.

Ta
b

le
1

. C
o

n
ti

n
u

ed

St
u

d
y

Ty
p

e
an

d
L

ev
el

o

f E
vi

d
en

ce
a

C
h

ar
ac

te
ri

st
ic

s
o

f
Sa

m
p

le
b

a
n

d
S

et
ti

n
g

Fi
n

d
in

g
s

Li
m

it
at

io
n

s

[email protected] AJN ▼ May 2022 ▼ Vol. 122, No. 5 27

M
ed

ia
n

a
g

e:
6

4–
68

y
ea

rs

Fe
m

al
e:

2
85

,6
52

M
al

e:
2

26
,7

41

Pr
em

ie
r P

er
sp

ec
ti

ve
d

at
a-

b
as

e
20

06
–2

01
6;

U

n
it

ed
S

ta
te

s

Re
su

lts
: M

M
A

re
g

im
en

s
fe

at
u

ri
n

g
o

n
e,

t
w

o,
o

r m
o

re
th

an
t

w
o

n
o

n
o

p
io

id

an
al

g
es

ic
s

w
er

e
as

so
ci

at
ed

w
it

h
s

te
p

w
is

e
p

o
si

ti
ve

e
ff

ec
ts

. P
at

ie
n

ts
h

av

in
g

h
ip

s
u

rg
er

y
w

h
o

re
ce

iv
ed

m
o

re
th

an
t

w
o

a
n

al
g

es
ic

s
ex

p
er

ie
n

ce
d

u
p

to

a
n

1
8.

5%
d

ec
re

as
e

in
o

p
io

id
p

re
sc

ri
p

ti
o

n
s

co
m

p
ar

ed
w

it
h

p
at

ie
n

ts

re
ce

iv
in

g
o

p
io

id
s

al
o

n
e.

S
im

ila
r r

es
u

lt
s

w
er

e
se

en
in

p
at

ie
n

ts
u

n
d

er
g

o
in

g

kn
ee

s
u

rg
er

ie
s.

N
SA

ID
s

an
d

C
O

X
-2

in
h

ib
it

o
rs

w
er

e
th

e
m

o
st

e
ff

ec
ti

ve

m
o

d
al

it
ie

s.
T

h
e

u
se

o
f n

o
n

o
p

io
id

s
w

as
a

ss
o

ci
at

ed
w

it
h

a
1

2%
d

ec
re

as
e

in

h
o

sp
it

al
L

O
S,

c
o

m
p

ar
ed

w
it

h
u

se
o

f o
p

io
id

s
al

o
n

e.

C
on

cl
us

io
ns

: T
h

e
u

se
o

f C
O

X
-2

in
h

ib
it

o
rs

a
n

d
N

SA
ID

s
si

g
n

ifi
ca

n
tl

y
d

ec
re

as
ed

o
p

io
id

re
q

u
ir

em
en

ts
a

n
d

h
o

sp
it

al
L

O
S.

P
at

ie
n

ts
re

ce
iv

in
g

t
w

o

o
r m

o
re

a
n

al
g

es
ic

s
h

ad
th

e
b

es
t r

es
u

lt
s.

R
af

iq
S

, e
t a

l.
20

14
24

R
an

d
o

m
iz

ed
c

o
n


tr

o
lle

d
s

tu
d

y,
o

p
en


la

b
el

d
es

ig
n

Le
ve

l I

15
1

p
at

ie
n

ts
u

n
d

er
g

o
in

g

ca
rd

ia
c

p
ro

ce
d

u
re

s
th

ro
u

g
h

m

ed
ia

n
s

te
rn

o
to

m
y

M
ea

n
a

g
e:

6
2–

64
y

ea
rs

Fe
m

al
e:

3
1

M
al

e:
1

20

B
M

I:
27

.4
–2

8.
1

H
o

sp
it

al
; D

en
m

ar
k

O
bj

ec
tiv

es
: T

o
e

va
lu

at
e

w
h

et
h

er
a

n
M

M
A

re
g

im
en

o
f d

ex
am

et
h

as
o

n
e,

g

ab
ap

en
ti

n
, i

b
u

p
ro

fe
n

, a
n

d
p

ar
ac

et
am

o
l o

ff
er

ed
b

et
te

r p
ai

n
re

lie
f w

it
h

fe

w
er

s
id

e
ef

fe
ct

s
th

an
a

tr
ad

it
io

n
al

re
g

im
en

o
f m

o
rp

h
in

e
an

d

p
ar

ac
et

am
o

l a
ft

er
c

ar
d

ia
c

su
rg

er
y.

Re
su

lts
: P

at
ie

n
ts

in
th

e
M

M
A

g
ro

u
p

u
se

d
s

ig
n

ifi
ca

n
tl

y
le

ss
m

o
rp

h
in

e
an

d

h
ad

s
ig

n
ifi

ca
n

tl
y

lo
w

er
p

ai
n

s
co

re
s

th
an

th
o

se
in

th
e

o
p

io
id

g
ro

u
p

. N
au


se

a
an

d
v

o
m

it
in

g
w

er
e

al
so

s
ig

n
ifi

ca
n

tl
y

re
d

u
ce

d
.

C
on

cl
us

io
ns

: M
M

A
re

su
lt

ed
in

b
et

te
r p

ai
n

re
lie

f w
it

h
fe

w
er

c
o

m
p

lic
at

io
n

s.

Th
e

st
u

d
y

w
as

c
o

n

d
u

ct
ed

a
t a

s
in

g
le

si

te
, w

h
ic

h
li

m
it

s
g

en
er

al
iz

ab
ili

ty
o

f
fin

d
in

g
s.

T
h

e
st

u
d

y
w

as
c

o
n

d
u

ct
ed

in

D
en

m
ar

k,
w

h
er

e
d

iff
er

en
t p

ro
to

co
ls

an

d
m

ed
ic

at
io

n
s

m
ay

b
e

u
se

d
.

W
ar

re
n

J
A

,
et

a
l.

20
17

30

R
et

ro
sp

ec
ti

ve
re

vi
ew

Le
ve

l I
II

12
3

p
at

ie
n

ts
u

n
d

er
g

o
in

g

o
p

en
v

en
tr

al
h

er
n

ia
re

p
ai

r

M
ea

n
a

g
e:

5
5.

8–
58

.5
y

ea
rs

Fe
m

al
e:

7
4

M
al

e:
4

9

A
m

er
ic

as
H

er
n

ia
S

o
ci

et
y

Q
u

al
it

y
C

o
lla

b
o

ra
ti

ve
d

at
ab

as
e;

U
n

it
ed

S
ta

te
s

O
bj

ec
tiv

es
: W

it
h

in
th

e
co

n
te

xt
o

f a
n

E
R

A
S

p
ro

to
co

l,
to

e
va

lu
at

e
th

e
ef

fe
ct

o

f M
M

A
o

n
o

p
io

id
u

se
a

ft
er

v
en

tr
al

h
er

n
ia

re
p

ai
r.

(M
M

A
c

o
n

si
st

ed
o

f p
re


o

p
er

at
iv

e
ac

et
am

in
o

p
h

en
, c

el
ec

o
xi

b
, a

n
d

o
xy

co
d

o
n

e;
in

tr
ao

p
er

at
iv

e
ke

t-
am

in
e,

li
d

o
ca

in
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28 AJN ▼ May 2022 ▼ Vol. 122, No. 5 ajnonline.com

investigated the effect of adding iv acetaminophen
to the perioperative pain management regimen.25
They found that doing so significantly reduced total
postoperative narcotic use: patients who received
perioperative iv acetaminophen used an average of
28.3 mg of opioids following surgery compared
with an average of 41.3 mg among patients who
did not. And in a before-and-after cohort study
among 248 patients undergoing surgery for hip
fracture, Girardot and colleagues explored the use
of a standardized order set calling for 1,000 mg of
oral acetaminophen before surgery and up to three
doses following surgery as a first-line treatment.27
Such use was found to reduce total postoperative
oral opioid use by 22.6%.

Similarly, iv ibuprofen given in addition to mor-
phine was shown to reduce the amount of morphine
needed for postoperative pain. In a multisite, double-
blind, randomized controlled trial among 206 patients
undergoing either orthopedic or abdominal surgery,
Gago Martínez and colleagues found that patients
who received iv ibuprofen every six hours needed
significantly less morphine than patients who received
placebo (14.22 mg versus 29.8 mg, respectively).21

IV acetaminophen and iv ibuprofen are often used
conjunctively in multimodal analgesia regimens. A
multisite randomized controlled trial by Gupta and
colleagues in 74 patients having elective hip or knee
arthroplasty found that, compared with administer-
ing iv ibuprofen alone, giving patients both drugs at
the start of surgery and then every six hours until dis-
charge for up to five days significantly lowered verbal
pain scores and opioid consumption.23 A prospective,
double-blind, randomized controlled trial by Daniels
and colleagues yielded similar findings.20 In that study,
patients who received iv ibuprofen and iv acetamino-
phen reported better pain scores and used less opioids
than those receiving either drug alone.

The combined use of NSAIDs with gabapentin
or celecoxib (a COX-2 inhibitor) has also shown
effectiveness in multimodal analgesia pain man-
agement strategies. Using such combinations,
Cozowicz and colleagues26 and Memtsoudis and
colleagues29 also found decreased opioid use in
their large population-based studies, in particular
with the addition of a COX-2 inhibitor. While

these studies lacked randomization and were not
experimental, their findings are supported by
other higher-level studies.

In a prospective randomized controlled
trial by Garcia and colleagues, using a com-
bination of pregabalin, a COX-2 inhibitor,
and extended-release oxycodone proved effec-
tive in improving pain scores and decreasing
iv morphine requirements in patients undergo-
ing lumbar decompression surgery.22 And in a
randomized controlled trial by Rafiq and col-
leagues, giving a combination of dexametha-
sone, gabapentin, ibuprofen, and paracetamol
to patients undergoing cardiac surgery through
sternotomy resulted in significantly less pain on

postoperative day 3 than was experienced by
those receiving morphine.24

One study evaluated the use of an ERAS protocol
in open ventral hernia repair surgeries.30 The proto-
col included several preoperative analgesics (pregab-
alin, acetaminophen, celecoxib, and oxycodone),
intraoperative analgesics (ketamine, with or without
lidocaine), and postoperative analgesics (ketamine,
ketorolac, acetaminophen, as well as oxycodone or
hydrocodone for breakthrough pain). Patients on
the ERAS protocol required significantly less opioid
on postoperative days 0, 1, and 2 than those on
other regimens.

Shorter hospitalizations. Another common out-
come of note was reduced hospital length of stay.
Multimodal analgesia strategies were found to
decrease respiratory and gastrointestinal complica-
tions29 and improve rates of participation in physi-
cal therapy and discharge to home.25 In the study
by Rafiq and colleagues, nausea and vomiting
occurred in no patients in the intervention group
compared with 13 in the control group24; and in
the study by Garcia and colleagues, the patients
receiving multimodal analgesia were able to
resume a regular diet sooner.22 Three studies found
that patients receiving multimodal analgesia had
overall shorter hospital lengths of stay.25, 26, 29 And a
study by Maiese and colleagues that compared
total hospital costs for surgical patients receiving
iv acetaminophen plus other iv analgesics with
those for surgical patients receiving iv opioid

In comparison with unimodal opioid therapy, multimodal

analgesia regimens were found to provide safe and effective

pain relief while lowering opioid requirements.

[email protected] AJN ▼ May 2022 ▼ Vol. 122, No. 5 29

monotherapy found that costs were significantly
lower for the former group ($12,540 versus $13,242,
respectively).28

Gupta and colleagues found that the com-
bined perioperative use of iv ibuprofen and iv
acetaminophen reduced time in the recovery
room but did not decrease hospital length of stay
overall.23 But given that participants in the con-
trol group also received perioperative iv ibupro-
fen, these results might suggest that adding one
iv nonopioid analgesic to the perioperative pain
regimen is sufficient.

Nurses’ perspectives. In the reviewed qualitative
study, Angelini and colleagues explored the perspec-
tives of nurses and other providers with regard to
postoperative pain management in patients having
lumbar spine surgery.31 The researchers noted that
such pain management has been shifting from “tra-
ditional” reliance on opioids toward multimodal
analgesia strategies. The nurses expressed frustra-
tion with “the ambiguity of wanting to alleviate
pain but not wanting to fuel an addiction,” and
spoke of feeling alone and powerless in their efforts
to promote comfort.31 But another finding was that
professionalism was a “balancing act” between
humility and confidence. The more experienced
providers could rely on their expertise to address
insufficient care; the less experienced had fewer pre-
conceived ideas about pain control and what was
possible.

Potential adverse effects. There were a few indica-
tions of concern. In evaluating the safety of multi-
modal analgesia regimens, Cozowicz and colleagues
found that including two or more nonopioids signif-
icantly increased the risks of postoperative delirium
and greater naloxone need.26 Gabapentin in particu-
lar was associated with greater naloxone need,
regardless of the strength of the prescribed opioids,
which suggested synergistic interactions between
gabapentinoids and opioids. Perhaps preemptively,
Gupta and colleagues excluded patients with aller-
gies to ibuprofen or acetaminophen; those taking
anticoagulants; and those with histories of impaired
liver, renal, or cardiac function.23 Rafiq and col-
leagues, on the other hand, found no significant
between-group differences in postoperative in-
hospital renal, cardiovascular, or gastrointestinal
complications.24

DISCUSSION
Experts in pain management have recommended
the use of multimodal analgesia strategies in the
management of acute pain.12, 33 The findings of this
review add strong support for such use among sur-
gical patients. In comparison with unimodal opioid
therapy, multimodal analgesia regimens were found
to provide safe and effective pain relief while lower-
ing opioid requirements. The use of multimodal
analgesia also decreased hospital lengths of stay
and, in the study that looked at economic impact,
lowered health care costs. It stands to reason that
multimodal analgesia has the potential to improve
patients’ quality of life, lower the risk of opioid mis-
use and addiction, and reduce resource utilization.

Indeed, as noted earlier, multimodal analgesia
has been a key part of ERAS protocols for more
than a decade, with acetaminophen and NSAIDs as
the mainstays.34 At least one state agency, the Ore-
gon Health Authority, in line with the Centers for
Disease Control and Prevention recommendations
for opioid-sparing management of chronic pain,35
has issued new practice guidelines that suggest the
use of nonopioid analgesics as first-line treatment
for acute pain.36 Several other states have adopted
guidelines for or limits to opioid prescription,37 thus
making the increased use of multimodal analgesia
strategies and ERAS protocols more likely. For a
number of surgical procedures, the use of ERAS
protocols has been shown to reduce postoperative

complications and hospital lengths of stay.34 In this
review, the study by Warren and colleagues, which
evaluated multimodal analgesia as part of an ERAS
protocol, supported those findings.30

Several studies investigated the use of more than
one nonopioid analgesic. Of note, the studies by
Gupta and colleagues and Daniels and colleagues
found that giving patients both iv acetaminophen
and iv ibuprofen improved pain scores and reduced
opioid requirements.20, 23 Such findings suggest that
combining two nonopioid analgesics in a multi-
modal analgesia regimen may be optimal. That
said, despite strong interest in opioid-sparing strat-
egies, many providers have had concerns about the
potential adverse effects of some nonopioid anal-
gesics included in multimodal analgesia regimens.
For example, in the reviewed studies, the finding
by Cozowicz and colleagues that adding two or

Three studies found that patients receiving multimodal analgesia

had overall shorter hospital lengths of stay.

30 AJN ▼ May 2022 ▼ Vol. 122, No. 5 ajnonline.com

more of certain nonopioids to a multimodal anal-
gesia regimen raised the risks of postoperative delir-
ium, and greater naloxone need indicates that more
research exploring specific nonopioid combinations
is warranted.26

Lastly, the qualitative findings by Angelini and
colleagues speak to the importance of better under-
standing the attitudes and beliefs of nurses and
other providers with regard to managing acute
postoperative pain. Despite a growing body of evi-
dence for the benefits of multimodal analgesia strat-
egies over opioids alone, many providers may still
be ambivalent or feel confused about the relevant
practice changes. More research is needed if we are
to choose appropriate tools to aid providers in
making the transition.

The MOSS: a clinical decision aid. The Michi-
gan Opioid Safety Score (MOSS), a relatively new
sedation scoring tool,5, 38 is to my knowledge the
only such tool that acknowledges multimodal
analgesia regimens. It’s designed to help nurses
conduct a safety assessment for patients receiving
postsurgical opioids as well as to increase the use
of multimodal analgesia. The tool’s developers
advise nurses “to ensure that patients never receive
opioid-only pain treatment regimens and that
patients ideally receive non-opioid analgesics . . .
on a continuous basis” while opioids are being
administered.5

The MOSS tool incorporates patient-specific risk
factors into sedation assessment for adverse conse-
quences38 such as unintended sedation and opioid-
induced respiratory depression. Scores are based on
a number of health risk factors that include having a
history of snoring, obesity, or obstructive sleep
apnea; undergoing abdominal or thoracic surgery;
anesthesia time of more than three hours within 24
hours of MOSS assessment; concomitant sedative
use within two hours of MOSS assessment; being
older than 75 years of age; and having a current his-
tory of smoking.5, 33, 38 The MOSS tool also assesses
for excessive sedation, using the modified Pasero
Opioid-Induced Sedation Scale, and guides the nurse
to stop opioids altogether in such cases.5 Possible
total scores thus range from 0 to 4, plus a STOP
override. Based on the score, the tool’s interpretation

section provides specific recommendations, which
include using multimodal analgesia, decreasing opi-
oid use, continuing opioid use with increased moni-
toring, and discontinuing all opioids.5

Yaldou and colleagues conducted a cross-
sectional survey to examine the MOSS tool’s reliabil-
ity and validity as well as its acceptance by nurses.38
The researchers found the tool to have excellent reli-
ability (intraclass correlation coefficient, 0.83) and
stated that, given the conditions of use, such reliabil-
ity signifies validity. Using the tool, participants chose
the appropriate clinical action an average of 80.5%
of the time; and 59% agreed that the tool positively
affected patient safety and improved their confi-
dence in using opioids. The researchers also reported
that nurses in their hospital system who used the

MOSS felt empowered to counteract requests or
demands for opioids when indications were that this
wasn’t safe.5

The MOSS tool was successfully implemented
in a quality improvement project led by Barber in
an intensive care setting.39 Compared with the pre-
intervention group, the postintervention group
showed a small reduction in naloxone administra-
tion (2.2% versus 3.3%) and a significant reduction
in rapid response calls (13.3% versus 30%). Barber
also noted improved nurse awareness of patients at
high risk for opioid-induced respiratory depression.
These results suggest that the MOSS tool is valid for
opioid sedation assessment and intervention and has
potential to improve patient outcomes and nurses’
confidence in managing acute pain in hospitalized
patients. Barber’s project includes a detailed road
map for implementing the tool in various practice
settings, but more research is needed before the tool
can be widely adopted.

Another tool worth mentioning is the Opioid
Risk Tool, a brief self-report questionnaire that
aims to assess a patient’s risk of developing addic-
tion with opioid use in primary care settings.40 It has
shown reliability and validity among patients in
chronic pain, and its effectiveness should also be
studied in the acute care setting. The identification
of patients at risk for developing opioid addiction
would create opportunities for tailored pain man-
agement regimens and patient education.

With the appropriate tools and education,

nurses can make the transition from traditional opioids to

multimodal analgesia strategies.

[email protected] AJN ▼ May 2022 ▼ Vol. 122, No. 5 31

Implications for nursing practice. Opioids
are commonly administered to patients in acute
care settings, but these drugs are associated with
serious complications, including respiratory
depression and death.33 For postsurgical patients,
opioid-related adverse events have reportedly
been found to increase hospital lengths of stay
by 55%, health care costs by 47%, and 30-day
readmission rates by 36%.33 Moreover, the use
of opioids in the inpatient setting is associated
with increased risk of dependency.41 According
to the National Institute on Drug Abuse, 21% to
29% of patients with chronic pain misuse pre-
scribed opioids and 8% to 12% develop opioid
misuse disorder.7 Perhaps a more startling sta-
tistic is that 80% of heroin users first misused
prescription opioids.7

Several studies in this review explored the use
of various nonopioid medications that can eas-
ily be administered by the bedside nurse and
that, when used together, often provide superior
pain relief than opioids alone.19, 21-25, 29 Yet despite
growing support from experts and new practice
guidelines, multimodal analgesia isn’t routinely
used by nurses to manage postoperative pain.
The qualitative study in this review by Angelini
and colleagues revealed nurses’ frustration and
concerns about the potential for opioid addic-
tion in their patients.31 Unless nonopioid medi-
cations are ordered and given on a routine basis,
opioids may continue to be first-line treatment.
For nurses to adopt multimodal analgesia, more
education and training are needed. Giving nurses
a user-friendly clinical decision aid such as the
MOSS tool, which by design emphasizes multi-
modal analgesia and empowers nurses in its use,
will facilitate practice change.

Recommendations. The opioid-sparing pharma-
cological interventions covered in this review have
been shown not only to reduce opioid use, but also
to improve pain scores while decreasing patients’
risk of many opioid-related complications. Hospital
leaders may want to consider the development of
standardized order sets or protocols that include
multimodal analgesia strategies,27 as well as the use
of a clinical decision aid that assists in their use.38
The MOSS tool shows promise, and further research
is recommended. Several medications that can be
readily used by the bedside nurse on either a sched-
uled or an as-needed basis are presented here, and
other high-quality studies specifically comparing one
analgesic with another can be found in the literature.
That said, further research regarding such analge-
sics, including their cost effectiveness, will be helpful
for hospital leaders.

As with any practice change, education for pro-
viders regarding the need for change is essential.
Nurses deserve to understand how the health care

system’s reliance on opioids to manage pain has
contributed to the opioid epidemic, as well as its
devastating effects on quality of life. Transitioning
to the use of nonopioid medications as first-line
pain management will mean seeing the bigger pic-
ture. Patients are accustomed to a health care sys-
tem that associates comfort with the generous use
of opioids to achieve a relatively pain-free state. As
nurses begin to transition to the use of multimodal
analgesia strategies, they may find themselves in
conflict with their patients, who will also have to
adjust their expectations. Having the necessary
education, tools, and administrative support will
empower nurses to implement these new strategies.
Adding organizational support through elements
already in the workflow, such as order sets, print
and digital education and trainings and reminders,
guidelines accessible in a patient’s chart, and appro-
priate tools (in particular, those developed by guide-
line developers42) can be vital to success and are
recommended.

Limitations. This review has some limitations.
First, although inclusive of both empirical and the-
oretical research, integrative reviews are typically
considered lower-level evidence, as they lack the
rigor associated with higher-level primary research
studies.18 Second, though I followed essential inte-
grative review methodology, I worked indepen-
dently. The addition of a second reviewer could
have minimized bias and strengthened the reliabil-
ity of the results. Lastly, of the 13 included stud-
ies, 12 were quantitative and only one was qualita-
tive. More qualitative research is essential if we are
to fully understand nurses’ experiences and perspec-
tives regarding multimodal analgesia and acute pain
management.

CONCLUSIONS
The findings of this review provide strong support
for the use of multimodal analgesia to treat acute
pain in surgical patients. Decreasing the opioid
requirements of and use by hospitalized patients
decreases their risk of dependency, misuse, and
addiction. Nurses don’t routinely use multimodal
analgesia as first-line treatment for managing
acute pain. Yet because bedside nurses typically
spend more time with patients than any other pro-
viders, they can have a much larger impact on the
opioid epidemic than they may realize. Providing
nurses with the necessary education, appropriate
decision tools, and collegial and organizational
support will help them make the crucial transition
from traditional opioids to multimodal analgesia
strategies. ▼

Jennifer René Tavernier is nursing faculty in the Health Professions
Division at Lane Community College, Eugene, OR. Contact author:
[email protected] The author has disclosed no potential conflicts
of interest, financial or otherwise.

32 AJN ▼ May 2022 ▼ Vol. 122, No. 5 ajnonline.com

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