Transdermal Buprenorphine for Acute Postoperative Pain: a Systematic

Home , Dermal patch

Rev Bras Anestesiol. 2020;70(4):419---428

SYSTEMATIC REVIEW

Transdermal buprenorphine for acute postoperative

pain: a systematic review

∗

Felipe Chiodini Machado , Gilson Carone Neto, Luisa Oliveira de Paiva,

Tamiris Cristina Soares, Ricardo Kenithi Nakamura, Leonardo de Freitas Nascimento,

Camila Sato Campana, Lia Alves Martins Mota Lustosa, Rachel Andrade Cortez,

Hazem Adel Ashmawi

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Departamento de Anestesiologia, São

Paulo, SP, Brazil

Received 21 January 2020; accepted 4 April 2020

Available online 20 June 2020

KEYWORDS Abstract

Buprenorphine; Background and objectives: Postoperative pain is still a major concern in several surgical pro-

Cutaneous cedures. Multimodal analgesia is best for postoperative pain management; however, opioid

administration; therapy is still the main treatment for pain after surgical procedures. Transdermal buprenor-

phine is a partial ␮-agonist opioid widely used for chronic pain syndromes, with limited evidence

Transdermal patch;

for acute postoperative pain. A systematic review of studies examining transdermal buprenor-

Postoperative pain;

phine for acute pain management after surgery was conducted.

Acute pain

Contents: Data from PubMed, Embase, The Cochrane Central Register of Controlled Trials (CEN-

TRAL), CINAHL via EBSCOhost, and LILACS were reviewed, including randomized clinical trials

that evaluated total postoperative pain, postoperative analgesic consumption, drug-related side

effects and patient satisfaction with analgesia regimen. Data from nine studies (615 patients)

were included in this review. Most studies initiated transdermal buprenorphine use 6 to 48 hours

before surgery, maintaining use from 1 to 28 days after the procedure. Most studies showed

lower or similar postoperative pain scores, postoperative analgesic consumption and patient

satisfaction comparing buprenorphine to placebo, tramadol, celecoxib, ﬂurbiprofen and pare-

coxib. The incidence of side effects varied between studies, with most showing no increase in

drug-related side effects with buprenorphine use, except one study, which compared buprenor-

phine to oral tramadol, and one to transdermal fentanyl. However, most results were derived

from evidence with an overall high or unclear risk of bias.

∗

Corresponding author.

E-mails: [email protected], [email protected] (F.C. Machado).

https://doi.org/10.1016/j.bjane.2020.06.009

license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

420 F.C. Machado et al.

Conclusions: Although more studies are necessary, initial results show that transdermal

buprenorphine seems to be an effective and safe opioid choice for management of acute

postoperative pain.

open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-

nc-nd/4.0/).

PALAVRAS-CHAVE Uso da buprenorﬁna transdérmica na dor aguda pós-operatória: revisão sistemática Buprenorﬁna;

Administrac¸ão Resumo

cutânea; Justiﬁcativa e objetivos: A dor pós-operatória ainda é uma queixa importante em vários pro-

Sistema cedimentos cirúrgicos. A analgesia multimodal é a melhor conduta para a dor pós-operatória,

transdérmico; embora a terapia com opioides ainda seja o principal tratamento para a dor após procedi-

mentos cirúrgicos. A buprenorﬁna transdérmica é um opioide agonista ␮ amplamente prescrito

Dor pós-operatória;

nas síndromes de dor crônica, mas com limitada evidência do seu uso para dor aguda no pós-

Dor aguda

operatório. Realizamos revisão sistemática de estudos que examinaram o papel da buprenorﬁna

transdérmica no tratamento da dor aguda pós-operatória.

Conteúdo: Revisamos os dados de PubMed, Embase, Registro Central de Ensaios Controlados

Cochrane (CENTRAL), CINAHL via EBSCOhost e LILACS, incluindo estudos clínicos randomiza-

dos que avaliaram a dor pós-operatória total, consumo de analgésicos pós-operatórios, efeitos

colaterais relacionados a medicamentos e satisfac¸ão do paciente com esquema de analgesia.

Dados de nove estudos (615 pacientes) foram incluídos nesta revisão. A maioria dos estudos ini-

ciou o uso transdérmico de buprenorﬁna 6 a 48 horas antes da cirurgia, mantendo o uso de 1 a

28 dias após o procedimento. A maioria dos estudos encontrou valores semelhantes ou menores

para o escore de dor pós-operatória, consumo pós-operatório de analgésicos e satisfac¸ão do

paciente quando a buprenorﬁna foi comparada ao placebo, tramadol, celecoxibe, ﬂurbiprofeno

e parecoxibe. A incidência de efeitos colaterais oscilou nos estudos, e a maioria não mostrou

aumento de efeito colateral relacionado ao uso de buprenorﬁna, exceto em dois estudos, um

que comparou buprenorﬁna ao tramadol oral e outro ao fentanil transdérmico. No entanto, a

maioria dos resultados foi obtida a partir de evidências com um risco geral alto ou risco de viés

impreciso.

Conclusões: Embora sejam necessários mais estudos, os resultados iniciais mostram que a

buprenorﬁna transdérmica parece ser uma forma de administrac¸ão segura e efetiva de opioide

no tratamento da dor aguda pós-operatória.

artigo Open Access sob uma licenc¸a CC BY-NC-ND (http://creativecommons.org/licenses/by-

nc-nd/4.0/).

Introduction Buprenorphine is a semisynthetic ␮-opioid receptor

(MOR) partial agonist and Kappa Opioid Receptor (KOR)

antagonist. Its unique pharmacodynamics results in a lower

In spite of recent developments in pain treatment, many

incidence of opioid-related side effects and risk of abuse

patients still undergo moderate to severe pain after surgery.

compared to other full MOR agonists. It also has a long dura-

It is estimated that severe postoperative pain is reported by

5 --- 7

tion of action due to its slow dissociation from MOR, being

20---40% of patients submitted to surgical procedures, espe-

1 75 to 100 times more potent than morphine, with a ceiling

cially abdominal, thoracic, orthopedic and pelvic surgeries.

5,8

effect on respiratory depression, but not on analgesia. It

Pain in the ﬁrst days after surgery can lead to delayed

is metabolized in the liver by cytochrome P450 to its active

ambulation, increase in cardiopulmonary and thrombotic

1,2 metabolite (norbuprenorphine). However, it can be elimi-

morbidity as well as the development of chronic pain.

nated through the biliary and urinary tract, therefore there

Multimodal analgesia is currently the best treatment for

is evidence that buprenorphine can be safely used in patients

acute postoperative pain, however opioid therapy is still

with renal impairment and should be carefully considered in

the main approach for the management of moderate to

5,7,9

3 patients with impaired liver function.

severe postoperative pain. Despite extensive use, opioids

Buprenorphine has been used as an analgesic for chronic

can lead to side effects such as nausea, vomiting, prolonged

7,9---11

pain and opioid withdrawal syndrome, but there is

ileus, sedation, urinary retention, respiratory depression

also evidence for use of buprenorphine in the postopera-

and addiction. In fact, the need for high opioid doses in the

tive period for the treatment of moderate to severe pain

postoperative period is related to higher incidence of side

4 in a variety of surgical procedures. Most acute uses of

effects and risk of opioid abuse.

Transdermal buprenorphine for acute pain 421

buprenorphine include epidural, intrathecal, intravenous, to be collected were difference in means in postoperative

sublingual, subcutaneous and intra-articular routes. Its high pain, rescue analgesic use, adverse effects and patient sat-

lipophilicity and low molecular weight make buprenorphine isfaction.

12,13

a suitable agent to use via the transdermal route. The

speciﬁc pharmacodynamics vary with each patch manufac-

Risk of bias assessment

turer, although most buprenorphine patches have an onset

of 12 to 24 hours, achieving approximately stable plasma

14 Risk of bias assessment was performed according to

concentrations on the third day after use. Its duration of

the following criteria for each study: selection bias

action is also prolonged after achieving a steady state, rang-

5,6,9 (random sequence generation, allocation concealment);

ing from 3 to 7 days. Such a route has been used for the

9,10,12 performance bias (blinding of participants and personnel);

treatment of chronic pain conditions, with some recent

detection bias (blinding of outcome assessment); attrition

studies investigating the use of perioperative transdermal

15---23 bias (incomplete outcome data); reporting bias (selec-

buprenorphine for the treatment of postoperative pain. 25

tive reporting); and others. According to the Cochrane

This article presents a systematic review regarding trans-

database, risk of bias can be graduated into high, low and

dermal buprenorphine use in patients submitted to surgical

unclear, with a high risk of bias considered when any of the

procedures, compared to other analgesics commonly used

previous items evaluated in the studies were not performed.

in the perioperative period or placebo. Outcomes accessed

When such items were assessed adequately, a low risk of bias

were postoperative pain, rescue analgesic use, adverse

was considered, whereas unclear risk of bias was considered

effects and patient satisfaction.

when the available information was insufﬁcient to classify

each item as high or low risk of bias, or was not properly

26,27

Methods reported in the article.

Search strategy Results

Literature was retrieved from PubMed, Embase via Ovid SP,

The initial search identiﬁed 386 potential studies. After

The Cochrane Central Register of Controlled Trials (CEN-

duplicates and irrelevant titles exclusion, 143 articles titles

TRAL), CINAHL via EBSCOhost, and LILACS. The last search

and abstracts were reviewed. During abstract review, 110

was conducted on April 2, 2019 with no limit date. The

studies were excluded for being case reports, case series,

search strategy included combinations of the keywords:

reviews, non-human research, language other than English

‘‘acute pain’’; ‘‘postoperative pain’’; ‘‘buprenorphine and

or Spanish, or presenting data about non-transdermal or

other opioids commonly used for perioperative analgesia’’

chronic buprenorphine use. The remaining 33 full-text arti-

(full strategy for MEDLINE in Appendix 1 --- Supplementary

cles were reviewed and a total of nine studies (615 patients)

Material). Free text words and controlled vocabulary/MeSH

were included in the systematic review. The PRISMA pro-

terms were combined without any limitation in the search

cess is detailed in Fig. 1 and a summary of studies contents

period. The MEDLINE search terms were adapted for each

is shown in Table 1. Surgical procedures included spine

database. Ad hoc searching was also performed; and the ref- 17,19,22 15 18

surgery, major and elective abdominal surgery,

erences from all included articles were manually searched 20,21 16

hysterectomy and myomectomy, hip surgery, and hal-

to identify additional articles. 23

lux valgus corrections. Transdermal buprenorphine was

started 6 to 48 hours before surgery in doses ranging from

−1 −115---18,22,23

Study selection and data collection 5 mcg h to 52.5 mcg h and maintained for 1 --- 7

days after the procedure. Only one study initiated transder-

The present review adhered to the recommendations of the mal buprenorphine 36 hours after surgery and maintained it

Preferred Reporting Items for Systematic review and Meta- for 28 days after the procedure. Control groups received

24 18---20 16,17

Analysis (PRISMA) protocol statement and is registered placebo, tramadol, a different dosage of transder-

18,20,21

in PROSPERO database (CRD42019131666). Inclusion crite- mal buprenorphine. Non-Steroidal Anti-Inﬂammatory

22,23 15

ria were: randomized controlled trials with a population of Drugs (NSAIDs) or transdermal fentanyl. The risk of bias

18 years-old or more, undergoing surgical procedures, use summary for included studies is shown in Fig. 2.

of transdermal buprenorphine in the perioperative period In six studies, buprenorphine was considered more

18---20 22,23 16

to treat acute pain, studies written in English or Spanish. effective than placebo, celecoxib and tramadol

Exclusion criteria included: case-reports, case series, animal for reducing postoperative pain scores. In three studies,

model studies, observational and cohort studies, transder- buprenorphine was considered as effective as tramadol,

22 23

mal buprenorphine used for non-acute postoperative pain. parecoxib and ﬂurbiprofen for reducing postoperative

Tw o authors performed the search, selected the relevant pain scores. In one study, buprenorphine led to higher VAS

articles according to the eligibility criteria, and performed scores than transdermal fentanyl. One study compared

data extraction and content analysis independently. Dis- 10 mg and 20 mg buprenorphine patches, ﬁnding lower pain

agreements were discussed with a third author. Available scores in the higher dose buprenorphine group. Other study

−1 −1

data was collected from the articles and outcomes exam- compared buprenorphine doses of 17.5 mcg h , 35 mcg h

−1

ined included postoperative pain, postoperative analgesic and 52.5 mcg h , while another study compared buprenor-

−1 −1 −1

consumption, drug-related side effects and patient satisfac- phine doses of 17.5 mcg h , 26.25 mcg h and 35 mcg h .

tion. When limited relevant data was available, an attempt There was no difference in postoperative pain scores with

20,21

to contact the authors was made. Summary measures aimed different buprenorphine dosages in both studies.

422 F.C. Machado et al. on on

celecoxib

buprenorphine group compared buprenorphine group both ﬂurbiprofen and X Higher satisfaction Higher satisfaction Patient satisfaction in group

for PONV

higher

signiﬁcant

PONV incidence tramadol buprenorphine doses. Conﬂicting results Increasing somnolence with No differences Drug-related side-effects Higher in

1. had total

and

during analgesic

7-days

difference

POD

lower analgesic consumption the consumption buprenorphine and ﬂurbiprofen groups Postoperative analgesic consumption buprenorphine group POD Lower follow-up in No X h 1

12 for POD

for POD

and

groups and group group

POD until 7

pain

no lower

to No in until

rest

after No to

movement: 2 higher lower PO

but at

rest: at lower

24 POD scores at

PO,

score score

but differences

h Pain

7. scores buprenorphine differences differences placebo buprenorphine 1 buprenorphine buprenorphine difference celecoxib. ﬂurbiprofen from from 24 movement. pain compared VAS PO Pain no Postoperative VAS

50 twice

groups day h

orally

I.V a 8 and

day

a every twice celecoxib 200 Placebo Control Flurbiprofen 50 Tramadol 7 PO

days day surgery surgery surgery

of 24 2 1 24 POD5 POD

until until until before before before administration From From From Form 1 1 − − h

1 1 1 h

− − − h h h

mcg

mcg mcg mcg

26.25 Buprenorphine doses 17.5 35 10 10

50 n 45 90

surgery

Surgical procedure Abdominal hysterectomy Hallux-valgus surgery Hip

characteristics.

Year 2018 2017 2018

Studies al.

1 et al.

et al.

Desai Table Author Rivera-Ruiz et Xu

Transdermal buprenorphine for acute pain 423 on

parecoxib

celecoxib

buprenorphine group compared both and X X Higher satisfaction Patient satisfaction significant significant significant

No No differences differences differences No Drug-related side-effects h

in 48

ﬁrst

were use

total to

in until

lower of POD

and

differences signiﬁcant

analgesic

PO consumption until buprenorphine group; frequency brupenorphine group use higher were rescue analgesia Time analgesic in differences No analgesic consumption No 3

VAS

in in

PO 14

group and in

POD pain Postoperative h

in 48

POD

groups lower 1.

analgesia h

until 0

POD

5 score

differences

and score differences buprenorphine parecoxib Buprenorphine from until Better VAS No twice

mg groups Postoperative day oral

orally

day

I.V. a and

day

once controlled- release a Placebo twice celecoxib 200 Control tramadol tablets 150-300 Parecoxib 40 after 5 PO

h h

h until

days

surgery surgery

of 36 24 2 48 POD

surgery POD until until before before administration From From From Form 1 1 1 1 1 1 − − − − − − h h h h

h h

mcg mcg mcg mcg

mcg mcg

10 Buprenorphine doses 5 15 20 10 5

96 n fusion 69 surgery 70

Spinal Spinal Lumbar discectomy procedure )

Year Surgical 2017 Continued (

al. 2017

al.

al. 2017 et

Tang Table Author Kim Niyogi

424 F.C. Machado et al. signiﬁcant

differences X X Patient satisfaction No Intravenous.

IV,

PO POD scores

Day; 3

buprenorphine placebo

in sedation in

> >

and

signiﬁcant mg mg 2

scores buprenorphine groups 1, with buprenorphine 20 Sedation Drug-related side-effects 10 until differences Higher No At to Postoperative

in in

PO. the

group

POD, until h

in > >

4, 48 PO higher

similar

signiﬁcant placebo mg mg h

buprenorphine dosage 72 POD ﬁrst placebo both buprenorphine groups No Postoperative analgesic consumption buprenorphine 10 analgesic requirement was but differences group buprenorphine 20 Analgesic requirements on Analgesic requirements inversely proportional Vomiting;

mg and

groups 20

pain

surgery and

score

Nausea placebo 7 2

1, VAS

> >

end POD

score

signiﬁcant mg

POD

Buprenorphine from until in group Postoperative VAS Higher No buprenorphine 10 differences buprenorphine

Postoperative

1 − PONV, groups

mcg

Scale;

Control Placebo Transdermal fentanyl 25 X Analog

7 3 PO

h surgery surgery surgery

Visual of night 6 12

POD POD 72

VAS,

until until until before before administration before From From From Form 1 1 − − 1 1 1 1 h h

− − − − h h h h

Postoperative; mcg mcg

mcg mcg mcg mcg

PO,

35 20 Buprenorphine doses 10 10 17,5 52,5

review.

n 90 60 45 systematic

the

Surgical procedure Elective abdominal surgery Major abdominal surgery Open hysterectomy, myomectomy )

included

Year 2016 2015 2012

Continued studies (

al. al.

al.

et et

Setti Table Author Kumar Arshad Summary

Transdermal buprenorphine for acute pain 425

Records identified through

database searching (n = 386) Identification

Records after removing duplicates and articles with irrelevant titles to the review (n = 143)

Abstract review:

Records e xcluded (n = 110)

Case r eports or case series

Screnning R eviews

Non- human research

Language ot her than English or

S panish

Chr onic use of Buprenorphine!

Non-tr ansdermal use of

B uprenorphine

Full-tex t articles excluded

Eligibility Full-tex t articles assessed (n = 24)

for eligibility Non-relev ant to the

(n = 33) review

St udies included in final

anal ysis synthesis

Included (n = 9)

Figure 1 PRISMA ﬂow diagram. From: Moher D, Liberati A, Tetzlaff J, Altman DG, the PRISMA Group (2009). Preferred reporting

items for systematic reviews and meta-analyses: the PRISMA Statement. PLoS Med 6(7): e1000097.

As for postoperative pain medications, ﬁve studies buprenorphine 20 mg > buprenorphine 10 mg > placebo,

showed lower rescue analgesic dosages in transdermal whereas two studies showed deeper sedation scores in

18,19 16 15 18

buprenorphine groups compared to placebo, tramadol buprenorphine group compared to fentanyl or placebo.

and celecoxib. Four studies showed no difference in Only four studies evaluated overall patient satisfaction

additional analgesia usage with transdermal buprenor- with analgesia, with three studies reporting that transder-

15 17,19

phine compared to transdermal fentanyl, tramadol, mal buprenorphine use led to higher patient satisfaction

22 23 16 22,23

celecoxib and ﬂurbiprofen. Tw o studies compared dif- than tramadol and NSAIDs, while one study showed

ferent doses of buprenorphine, in one the rescue analgesic no signiﬁcant difference between different buprenorphine

−1 −1 −1 21

consumption was higher in patients receiving 10 mcg h dosages ranging from 17.5 mcg h to 52.5 mcg h .

−1 18

than in patients receiving 20 mcg h , while in the other

study rescue analgesic consumption decreased and trans-

−1 Discussion

dermal buprenorphine dosage increased from 17.5 mcg h

−1 −1 21

to 32 mcg h and 52.5 mcg h .

This is the ﬁrst review to assess transdermal buprenor-

Most studies reported a similar incidence of adverse

phine use for acute postoperative pain, including data

effects between transdermal buprenorphine and

18,19 17 22,23 from 615 patients undergoing several surgical procedures

placebo, tramadol, NSAIDs, or between dif-

in the qualitative analysis. Most studies initiated transder-

ferent doses of transdermal buprenorphine (10 mg vs.

−1 −1 −1 18,21 mal buprenorphine use 6---48 hours prior to surgery, which

20 mg; 17.5 mcg h , 32 mcg h or 52.5 mcg h ). One

is consistent with a 12---24 hours latency time for trans-

study showed higher Postoperative Nausea and Vomiting

5,6,9

dermal buprenorphine patches. Time to achieve stable

(PONV) in the tramadol control group than in the buprenor-

16 plasma concentrations would be ideal before a surgical

phine group, another reported more somnolence with

procedure, however, initiation of opioid use far before

426 F.C. Machado et al.

study, the buprenorphine patch was initiated 24 hours before

surgery, while the other study initiated buprenorphine or

tramadol 36 hours after surgery, with both groups using

Patient Controlled Analgesia (PCA) with fentanyl. The onset

of analgesia with buprenorphine is signiﬁcantly slower com-

pared to tramadol, therefore similar pain scores and PCA

opioid consumption could favor buprenorphine.

When compared to NSAIDs, transdermal buprenorphine

had similar postoperative pain scores to I.V. NSAIDs (ﬂur-

biprofen and parecoxib) and lower postoperative pain scores

than oral celecoxib. Also, the buprenorphine group had

similar postoperative analgesic consumption compared to

22,23

ﬂurbiprofen, parecoxib and celecoxib, except in one

study that showed lower consumption with buprenorphine

compared to celecoxib. No differences in drug-related

side effects were reported and both studies showed higher Random sequence generation (selection bias) Random sequence generation Allocation concealment (selection bias) Blinding of participants bias) and personnel (performance Blinding of outcome assessment detection bias) Incomeplete outcome data (attrition bias) Other bias

Selective reportingSelective (resporting bias)

satisfaction in the buprenorphine group, suggesting that

Arshad 2015 buprenorphine has similar or superior analgesic efﬁcacy than

Desai 2017 ﬂurbiprofen, parecoxib and celecoxib, with better patient

satisfaction and similar drug-related side effects.

Kim 2017

The only study that showed buprenorphine inferiority for

Kumar 2016 postoperative pain compared transdermal buprenorphine

−1 −1

10 mcg h and transdermal fentanyl 25 mcg h . However, in

Niyogi 2017

this study postoperative opioid consumption was similar and

Rivera-Ruiz 2018 the buprenorphine group reported higher pain and sedation

scores. Also, this study used non-equivalent buprenor-

Setti 2012 9,13,30

phine and fentanyl dosages, both patches were applied

Tang 2017 6 hours before surgery, allowing a wider transdermal fen-

Xu 2018 tanyl onset of action, but not an adequate buprenorphine

onset of action.

Three studies compared different dosages of

Figure 2 Risk of bias summary.

18,20,21

buprenorphine. In one study comparing buprenor-

phine dosages of 10 mg vs. 20 mg, pain scores were higher

a surgical procedure can raise ethical concerns regarding in the 10 mg group, while there were no differences in

20,21

unnecessary opioid usage before pain stimuli. There was pain scores in two studies comparing higher buprenor-

−1 −1

a large variation in the dosage of buprenorphine, ranging phine dosages (17.5 mcg h to 52.5 mcg h ). Tw o studies

−1 −1

from 5 mcg h to 52.5 mcg h . Nevertheless, most studies reported postoperative opioid consumption comparing doses

−1 −1

used 5 to 10 mcg h buprenorphine patches, representing of transdermal buprenorphine ranging from 10 mcg h to

−1 −1

an equivalent oral morphine dose of up to 30 mg day . 52.5 mcg h and, in both, analgesic requirements were

This dosage is compatible with most postoperative opioid inversely proportional to buprenorphine dosage. Studies

20 18

requirements and can be achieved even with weak opioid also showed increasing somnolence or sedation scores

1,28,29

intake regimens. with higher buprenorphine dosages, while one study showed

All studies comparing transdermal buprenorphine with no difference in side effects. One study reported no signif-

placebo showed lower postoperative pain scores and lower icant difference in patient satisfaction with buprenorphine

−1 −1 21

postoperative analgesic consumption in the buprenorphine dosages ranging from 17.5 mcg h to 52.5 mcg h . These

18---20 18

groups. Tw o studies showed increased sedation scores, results suggest that transdermal buprenorphine dosages can

nausea or somnolence in the buprenorphine group, while increasingly reduce postoperative analgesic requirements,

one study showed no differences in drug-related side while possibly leading to higher drug-related side effects

19 −1 −1

effects. It is well known that opioid usage reduces post- until 17.5 mcg h to 20 mcg h dosages. Higher dosages did

operative pain and postoperative analgesic consumption, not demonstrate an increased analgesic beneﬁt. Moreover,

1,28,29

while increasing drug-related side effects. In the no study reported severe or life-threatening side effects,

−1 −1

present review, buprenorphine did improve pain manage- suggesting that doses of 10 mcg h to 52.5 mcg h are

ment compared to placebo with evidence of increased relatively safe.

nausea, somnolence and sedation scores, but no difference The reported results are derived from few clinical tri-

to placebo was reported in other common opioid-related als, so more studies are necessary to conﬁrm the safety

side effects such as vomiting, pruritus, constipation, urinary and efﬁcacy of buprenorphine compared to other analgesics

retention and respiratory depression. or different buprenorphine dosages for postoperative pain.

Studies comparing transdermal buprenorphine to tra- Also, most multiple buprenorphine dosages studies used

20,21

madol, a weak opioid drug, favored buprenorphine or fractions of the buprenorphine patch, which is not rec-

showed similar results regarding postoperative pain scores, ommended by manufacturers.

analgesic consumption, drug side effects and patient Possible advantages of buprenorphine use over other

16,17

satisfaction. However, in the buprenorphine-favoring opioids include less association with analgesic tolerance

Transdermal buprenorphine for acute pain 427

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