nursing dimension

profiletitiorans
Original_Research__Combating_the_Opioid_Epidemic.18.pdf

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 e

n ti

fi ca

ti o

n S

cr e

e n

in g

E li

g ib

il it

y In

cl u

d e

d

Records identified through initial search of databases (n = 131)

and Google Scholar (n = 7)

Records screened (n = 136)

Full-text articles sought for retrieval (n = 28)

Full-text articles assessed for eligibility (n = 25)

Full-text articles not avail- able for retrieval (n = 3)

Studies included in integrative review (n = 13)

Full-text articles excluded (n = 12) •   Outcomes not related to

effects of multimodal analgesia

•   Study sample demograph- ics (outpatient surgery)

Records removed for duplication or other reasons (n = 2)

Records excluded (n = 108) •   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

Ta b

le 1

. S u

m m

ar y

o f S

tu d

ie s

R ev

ie w

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

A lt

u n

D , e

t a l.

20 17

19

Pr o

sp ec

ti ve

, r an

d o

m -

iz ed

, d o

u b

le -b

lin d

cl

in ic

al s

tu d

y

Le ve

l 1

50 p

at ie

n ts

u n

d er

g o

in g

el

ec ti

ve C

A B

G

M ed

ia n

a g

e: 6

2. 6–

66 .3

ye

ar s

Fe m

al e:

1 8

M

al e:

3 2

Si n

g le

-in st

it u

ti o

n te

rt ia

ry

h o

sp it

al ; T

u rk

ey

O bj

ec tiv

es : T

o c

o m

p ar

e th

e ef

fe ct

s o

f o ra

l t ra

m ad

o l a

n d

p ar

ac et

am o

l i n

co

m b

in at

io n

o n

m o

rp h

in e

co n

su m

p ti

o n

fo llo

w in

g C

A B

G .

Re su

lts : T

h e

g ro

u p

re ce

iv in

g P

C A

m o

rp h

in e

p lu

s o

ra l t

ra m

ad o

l a n

d

p ar

ac et

am o

l u se

d le

ss c

u m

u la

ti ve

m o

rp h

in e

th an

th e

g ro

u p

re ce

iv in

g

P C

A m

o rp

h in

e p

lu s

p la

ce b

o. T

o ta

l m o

rp h

in e

u se

d a

s “ re

sc u

e” a

n al

g es

ia

w as

a ls

o h

ig h

er in

th e

p la

ce b

o g

ro u

p .

C on

cl us

io ns

: T ra

m ad

o l a

n d

p ar

ac et

am o

l i n

c o

m b

in at

io n

a lo

n g

w it

h P

C A

m

o rp

h in

e im

p ro

ve s

an al

g es

ia a

n d

re d

u ce

s m

o rp

h in

e re

q u

ir em

en t u

p to

50

% c

o m

p ar

ed w

it h

m o

rp h

in e

P C

A a

lo n

e.

Th e

st u

d y’

s re

la -

ti ve

ly s

m al

l s am

p le

si

ze a

n d

s in

g le

-s it

e se

tt in

g li

m it

g en

er -

al iz

ab ili

ty o

f f in

d -

in g

s. T

h e

st u

d y

w as

co

n d

u ct

ed in

T u

r- ke

y, w

h er

e d

iff er

en t

p ro

to co

ls m

ay b

e u

se d

.

A n

g el

in i E

, et

a l.

20 20

31

Q u

al it

at iv

e st

u d

y

Le ve

l I II

9 h

ea lt

h c

ar e

p ra

ct it

io n

er s:

3

R N

s, 3

p h

ys ic

ia n

s, 3

p

h ys

io th

er ap

is ts

A g

e ra

n g

e: 2

9– 61

y ea

rs

Fe m

al e:

6 M

al e:

3

H o

sp it

al ; S

w ed

en

O bj

ec tiv

es : T

o e

xp lo

re a

n d

d es

cr ib

e h

ea lt

h c

ar e

p ra

ct it

io n

er s’

ex p

er ie

n ce

in

p o

st o

p er

at iv

e p

ai n

m an

ag em

en t.

Re su

lts : T

h re

e th

em es

e m

er g

ed :

1. C

o n

n ec

ti n

g w

it h

p at

ie n

ts is

v it

al t

o p

ai n

m an

ag em

en t.

2. P

ro fe

ss io

n al

is m

is a

b al

an ci

n g

a ct

b et

w ee

n v

u ln

er ab

ili ty

a n

d

st re

n g

th .

3. C

o lla

b o

ra ti

o n

r eq

u ir

es b

ei n

g c

o n

st an

tl y

re sp

o n

si ve

t o

t h

e en

vi ro

n -

m en

t.

C on

cl u

si on

s: H

ea lt

h c

ar e

o rg

an iz

at io

n s

m u

st “b

u ild

s tr

u ct

u re

s” t

h at

en

ab le

p ra

ct it

io n

er s

to d

el iv

er a

d eq

u at

e p

ai n

m an

ag em

en t

an d

th

at a

ck n

o w

le d

g e

th ei

r “ d

el ic

at e

si tu

at io

n w

h en

fa ci

n g

p at

ie n

ts in

p

ai n

.”

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.

G

re at

er re

p re

se n

ta -

ti o

n o

f n u

rs es

(a n

d

n u

rs e

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

tí 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 e,

o r b

o th

; p o

st o

p er

at iv

e ke

ta m

in e,

k et

o ro

la c,

a n

d a

ce t-

am in

o p

h en

; s o

m e

p at

ie n

ts a

ls o

re ce

iv ed

e p

id u

ra l a

n es

th es

ia .)

Re su

lts : T

h e

g ro

u p

re ce

iv in

g th

e fu

ll M

M A

re g

im en

w it

h e

p id

u ra

l a n

es th

e- si

a h

ad s

ig n

ifi ca

n tl

y re

d u

ce d

o p

io id

re q

u ir

em en

ts o

n p

o st

o p

er at

iv e

d ay

s 0,

1 , a

n d

2 ; a

n d

P C

A u

se w

as “n

ea rl

y el

im in

at ed

.”

C on

cl us

io ns

: T h

e u

se o

f M M

A , w

h ic

h ta

rg et

s m

u lt

ip le

s it

es a

lo n

g th

e p

ai n

p

at h

w ay

, i s

ef fe

ct iv

e in

d ec

re as

in g

o p

io id

c o

n su

m p

ti o

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

.

B M

I = b

o d

y m

as s

in d

ex ; C

A B

G =

c o

ro n

ar y

ar te

ry b

yp as

s g

ra ft

in g

; C O

X -2

= c

yc lo

o xy

g en

as e

2; E

R A

S =

e n

h an

ce d

r ec

o ve

ry a

ft er

s u

rg er

y; L

O S

= le

n g

th o

f s ta

y; M

M A

= m

u lt

im o

d al

a n

al g

es ia

; N SA

ID =

n o

n st

er o

id al

a n

ti in

fla m

- m

at o

ry d

ru g

; O M

E =

o ra

l m o

rp h

in e

eq u

iv al

en t;

P C

A =

p at

ie n

t- co

n tr

o lle

d a

n al

g es

ia .

a Pe

r th

e Jo

h n

s H

o p

ki n

s Ev

id en

ce L

ev el

a n

d Q

u al

it y

G u

id e

(w w

w .h

o p

ki n

sm ed

ic in

e. o

rg /e

vi d

en ce

-b as

ed -p

ra ct

ic e/

_d o

cs /a

p p

en d

ix _c

_e vi

d en

ce _l

ev el

_q u

al it

y_ g

u id

e. p

d f)

. b M

ea n

o r

m ed

ia n

a g

e ra

n g

es r

ef le

ct r

an g

e ac

ro ss

s tu

d y

g ro

u p

s. S

o m

e st

u d

ie s

d id

n o

t cl

ea rl

y re

p o

rt p

ar ti

ci p

an ts

’ s ex

.

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

REFERENCES 1. Jungquist CR, et al. Assessing and managing acute pain: a

call to action. Am J Nurs 2017;117(3 Suppl 1):S4-S11. 2. Gauchan S. Pain assessment in emergency department of

teaching hospital in Lalitpur. Journal of Karnali Academy of Health Sciences 2018;2(3):209-13.

3. Baker DW. The Joint Commission’s pain standards: origin and evolution. Oakbrook Terrace, IL: Joint Commission; 2017 May 5. https://www.jointcommission.org/-/media/tjc/ documents/resources/pain-management/pain_std_history_ web_version_05122017pdf.pdf.

4. Veterans Health Administration, Geriatrics and Extended Care Strategic Healthcare Group. Pain as the 5th vital sign toolkit (revised edition). Washington, DC; 2000 Oct. https:// www.va.gov/painmanagement/docs/pain_as_the_5th_vital_ sign_toolkit.pdf.

5. Soto R, Yaldou B. The Michigan Opioid Safety Score (MOSS): a patient safety and nurse empowerment tool. J Perianesth Nurs 2015;30(3):196-200.

6. National Institute on Drug Abuse. Opioids. n.d. https:// www.drugabuse.gov/drug-topics/opioids.

7. National Institute on Drug Abuse. Opioid overdose crisis. Bethesda, MD: National Institutes of Health; 2021 Mar 11. https://www.drugabuse.gov/drug-topics/opioids/opioid- overdose-crisis.

8. Centers for Disease Control and Prevention. Understanding the epidemic. Atlanta, GA; 2021 Mar 17. Opioids; https:// www.cdc.gov/opioids/basics/epidemic.html.

9. Centers for Disease Control and Prevention. Drug overdose deaths. 2021. https://www.cdc.gov/drugoverdose/deaths/ index.html.

10. AAFP News. AAFP, ACP release new acute pain clinical guideline. Ann Fam Med 2020;18(6):565-6.

11. American College of Surgeons, Committee on Trauma. Best practices guidelines for acute pain management in trauma patients. Chicago, IL; 2020 Nov. ACS trauma quality pro- grams; https://www.facs.org/-/media/files/quality-programs/ trauma/tqip/acute_pain_guidelines.ashx.

12. Hsu JR, et al. Clinical practice guidelines for pain manage- ment in acute musculoskeletal injury. J Orthop Trauma 2019; 33(5):e158-e182.

13. Beverly A, et al. Essential elements of multimodal analge- sia in enhanced recovery after surgery (ERAS) guidelines. Anesthesiol Clin 2017;35(2):e115-e143.

14. Melnyk M, et al. Enhanced recovery after surgery (ERAS) protocols: time to change practice? Can Urol Assoc J 2011; 5(5):342-8.

15. Savitha KS, et al. The effect of multimodal analgesia on intra- operative morphine requirement in lumbar spine surgeries. Anesth Essays Res 2017;11(2):397-400.

16. Savarese JJ, Tabler NG, Jr. Multimodal analgesia as an alter- native to the risks of opioid monotherapy in surgical pain management. J Healthc Risk Manag 2017;37(1):24-30.

17. Vila H, Jr., et al. The efficacy and safety of pain management before and after implementation of hospital-wide pain man- agement standards: is patient safety compromised by treat- ment based solely on numerical pain ratings? Anesth Analg 2005;101(2):474-80.

18. Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs 2005;52(5):546-53.

19. Altun D, et al. The effect of tramadol plus paracetamol on consumption of morphine after coronary artery bypass graft- ing. J Clin Anesth 2017;36:189-93.

20. Daniels SE, et al. Efficacy and safety of an intravenous acetaminophen/ibuprofen fixed-dose combination after bunionectomy: a randomized, double-blind, factorial, pla- cebo-controlled trial. Clin Ther 2019;41(10):1982-95.e8.

21. Gago Martínez A, et al. Intravenous ibuprofen for treatment of post-operative pain: a multicenter, double blind, placebo- controlled, randomized clinical trial. PLoS One 2016;11(5): e0154004.

22. Garcia RM, et al. A multimodal approach for postoperative pain management after lumbar decompression surgery: a prospec- tive, randomized study. J Spinal Disord Tech 2013;26(6):291-7.

23. Gupta A, et al. A randomized trial comparing the safety and efficacy of intravenous ibuprofen versus ibuprofen and acetaminophen in knee or hip arthroplasty. Pain Physician 2016;19(6):349-56.

24. Rafiq S, et al. Multimodal analgesia versus traditional opiate based analgesia after cardiac surgery, a randomized con- trolled trial. J Cardiothorac Surg 2014;9:52.

25. Bollinger AJ, et al. Is scheduled intravenous acetaminophen effective in the pain management protocol of geriatric hip fractures? Geriatr Orthop Surg Rehabil 2015;6(3):202-8.

26. Cozowicz C, et al. Multimodal pain management and postoperative outcomes in lumbar spine fusion surgery: a population-based cohort study. Spine (Phila Pa 1976) 2020; 45(9):580-9.

27. Girardot K, et al. Effectiveness of multimodal pain therapy on reducing opioid use in surgical geriatric hip fracture patients. J Trauma Nurs 2020;27(4):207-15.

28. Maiese BA, et al. Hospitalization costs for patients under- going orthopedic surgery treated with intravenous acet- aminophen (IV-APAP) plus other IV analgesics or IV opioid monotherapy for postoperative pain. Adv Ther 2017;34(2): 421-35.

29. Memtsoudis SG, et al. Association of multimodal pain man- agement strategies with perioperative outcomes and resource utilization: a population-based study. Anesthesiology 2018; 128(5):891-902.

30. Warren JA, et al. Effect of multimodal analgesia on opioid use after open ventral hernia repair. J Gastrointest Surg 2017;21(10):1692-9.

31. Angelini E, et al. Healthcare practitioners’ experiences of postoperative pain management in lumbar spine surgery care: a qualitative study. J Clin Nurs 2020;29(9-10): 1662-72.

32. Pitchon DN, et al. Updates on multimodal analgesia for orthopedic surgery. Anesthesiol Clin 2018;36(3):361-73.

33. Jungquist CR, et al. Monitoring hospitalized adult patients for opioid-induced sedation and respiratory depression. Am J Nurs 2017;117(3 Suppl 1):S27-S35.

34. Wainwright TW, et al. Consensus statement for periopera- tive care in total hip replacement and total knee replacement surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations. Acta Orthop 2020;91(1):3-19.

35. Dowell D, et al. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep 2016;65(1):1-49.

36. Oregon Health Authority, Public Health Division. Oregon acute opioid prescribing guidelines: recommendations for patients with acute pain not currently on opioids. Salem, OR; 2018 Oct. OHA 8297 (10/2018). https://www.oregon.gov/ osbn/Documents/Resource_OregonAcuteOpioidPrescribing Guidelines.pdf.

37. National Conference of State Legislatures. Prescribing poli- cies: states confront opioid overdose epidemic. Washington, DC; 2019 Jun 30. https://www.ncsl.org/research/health/ prescribing-policies-states-confront-opioid-overdose- epidemic.aspx.

38. Yaldou B, et al. Inter-rater reliability and reception of the Michigan Opioid Safety Score. J Perianesth Nurs 2018;33(4): 412-9.

39. Barber LE. Implementation of the Michigan Opioid Safety Score at community regional medical center [doctoral disser- tation]. Irvine, CA: Brandman University, Marybelle and S. Paul Musco School of Nursing and Health Professions 2018.

40. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med 2005;6(6):432-42.

41. Wardhan R, Chelly J. Recent advances in acute pain man- agement: understanding the mechanisms of acute pain, the prescription of opioids, and the role of multimodal pain therapy. F1000Res 2017;6:2065.

42. Flodgren G, et al. Tools developed and disseminated by guideline producers to promote the uptake of their guide- lines. Cochrane Database Syst Rev 2016;(8):CD010669.

  • 20220500.0-00018.pdf
    • AJN0522.OR.Tavernier.pdf