Anae12823

Review Article

A systematic review and meta-analysis of perineural

dexamethasone for peripheral nerve blocks

E. Albrecht,1 C. Kern2 and K. R. Kirkham3

1 Program Director of Regional Anaesthesia, 2 Professor and Head, Department of Anaesthesia, Centre HospitalierUniversitaire Vaudois and University of Lausanne, Lausanne, Switzerland3 Lecturer, Department of Anaesthesia and Pain Management, Toronto Western Hospital, University of Toronto,Toronto, Ontario, Canada

SummaryWe systematically reviewed the safety and efficacy of perineural dexamethasone as an adjunct for peripheral nerve

blockade in 29 controlled trials of 1695 participants. We grouped trials by the duration of local anaesthetic action

(short- or medium- vs long-term). Dexamethasone increased the mean (95% CI) duration of analgesia by 233

(172–295) min when injected with short- or medium-term action local anaesthetics and by 488 (419–557) min when

injected with long-term action local anaesthetics, p < 0.00001 for both. However, these results should be interpreted

with caution due to the extreme heterogeneity of results, with I2 exceeding 90% for both analyses. Meta-regression

did not show an interaction between dose of perineural dexamethasone (4–10 mg) and duration of analgesia

(r2 = 0.02, p = 0.54). There were no differences between 4 and 8 mg dexamethasone on subgroup analysis..................................................................................................................................................................

Correspondence to: E. Albrecht

Email: [email protected]

Accepted: 8 July 2014

IntroductionModerate to severe pain after orthopaedic surgery

can be reduced by regional neural blockade with

local anaesthetic [1]. Interventions that increase the

duration of local anaesthetic action could prolong

postoperative patient comfort [2]. Perineural cathe-

ters have been used to extend the duration of anal-

gesia but may be accompanied by catheter

migration, anaesthetic leakage or pump malfunction,

requiring complex logistic organisation [3], particu-

larly following ambulatory surgery. Several adjuncts,

including opioids, tramadol, clonidine and neostig-

mine, have been tested with single-shot regional

techniques, but have failed to achieve desired results

[2, 4].

Dexamethasone, a high-potency, long-acting gluco-

corticoid with little mineralocorticoid effect, has been

shown to prolong peripheral nerve blockade in animals

[5–8] and, when added to bupivacaine microspheres,

to extend the duration of analgesia in humans [9, 10].

Although incompletely understood, dexamethasone’s

mechanism of action may stem from decreased noci-

ceptive C-fibre activity via a direct effect on glucocorti-

coid receptors [11] and inhibitory potassium channels

[12]. Other authors suggest a local vasoconstrictive

effect, resulting in reduced local anaesthetic absorption

[13, 14], or a systemic anti-inflammatory effect [15]

following vascular uptake of the drug [16].

The results of several articles support the conten-

tion that perineural dexamethasone prolongs analgesia

© 2014 The Association of Anaesthetists of Great Britain and Ireland 71

Anaesthesia 2015, 70, 71–83 doi:10.1111/anae.12823

[16–21]. The objective of this meta-analysis was to

define the analgesic efficacy of dexamethasone as a

local anaesthetic adjunct for peripheral nerve blockade

and its potential role in clinical practice.

MethodsWe followed the PRISMA guideline [22]. We searched

the following databases without language restriction to

May 16th 2014: PUBMED; CENTRAL; Embase. We

used the following search terms: (an*esthetic technique

OR an*esthesia conduction OR local an*esthetics OR

(peripheral) nerve block OR regional an*esthesia)

AND (dexamethasone OR glucocorticoids OR ste-

roids). We used the following keywords: anaesth*,

anesth*, nerve*, dexamethas*, glucocort*, steroid*,

clinical*, random*, trial*. Retrieved articles were lim-

ited with ‘Clinical trials’ OR ‘Random allocation’ OR

‘Therapeutic use’. In addition, we searched by hand the

references of retrieved articles for additional relevant

trials. We also searched Google ScholarTM by entering

the aforementioned search terms. We included rando-

mised controlled trials (RCTs) that compared perineu-

ral local anaesthetics without vs with dexamethasone

for peripheral nerve blockade. We excluded RCTs of

dexamethasone: vs other adjuncts [23]; in intravenous

regional anaesthesia [24, 25]; when injected in all par-

ticipants [26]; when authors replicated results [27] of a

previously published study [28]; or when the full article

was not available and the abstract did not include the

necessary information [29].

Two authors (EA and KK) independently

extracted: types of surgery, regional block and injection

technique; type, concentration and volume of local

anaesthetic injectate; dose of dexamethasone; possible

combination with neuraxial or general anaesthesia;

other postoperative analgesic modalities; and duration

of analgesic effect. Each used the Cochrane Collabora-

tion’s risks of bias tool to assess retrieved RCTs [30]; a

third author (CK) resolved disagreements. The primary

outcome was duration of analgesia or sensory block

and was defined as time from injection, or the onset of

sensory blockade to pain or first analgesic request. If

several doses of dexamethasone were studied against a

control group, we included data from the group with

the highest dose. We grouped interventions in RCTs

by duration of local anaesthetic action: short- and

medium- (lidocaine, mepivacaine and prilocaine) vs

long-term action (bupivacaine, levobupivacaine and

ropivacaine). Mixtures of anaesthetics with short- and

long-term action were categorised as long-acting. We

extracted the onset times of sensory and motor block-

ades, the duration of motor blockade and rates of

block failure. We defined onset of sensory and motor

blockades as the time from completion of local anaes-

thetic injection to complete blockade. We also analysed

pain scores at rest and on movement, and cumulative

intravenous morphine consumption, grouped within

three postoperative periods (0–2, 8–12 or at 24 h). We

also recorded: the highest rate of nausea or vomiting

on the first postoperative day; the rate of pruritus;

patient satisfaction; and adverse effects associated with

dexamethasone, including hyperglycaemia, infection

and neurological complications.

We extracted means (SD or SEM or 95% CI) for

continuous variables, or estimated their values from

median (IQR) [31] when authors were unable to pro-

vide these data. We converted administered opioid into

equianalgesic doses of intravenous morphine [32],

while we standardised pain and satisfaction scores to a

0–100 analogue scale. We calculated pooled estimates

for two or more RCTs with a random-effects model,

presented as mean differences or relative risks with

their 95% CI. We also analysed the primary outcome

with a fixed-effect model. We employed the I2 value to

define low (25–49%), moderate (50–74%) and extreme

(> 74%) heterogeneity [33] and applied Egger’s test to

assess funnel plot asymmetry [34]. We performed

meta-regression for the interaction between dexameth-

asone dose and duration of analgesia or sensory block,

further exploring this through a subgroup analysis

according to the dose of dexamethasone. The software

we used for analyses was: Review Manager (RevMan

version 5.2; Copenhagen, The Nordic Cochrane Cen-

tre, The Cochrane Collaboration 2012); Comprehen-

sive Meta-analysis (Version 2; Biostat, Englewood, NJ,

USA) and JMP 9 statistical package (SAS Institute,

Cary, NC, USA). We considered a two-sided p < 0.05

significant.

ResultsWe included 29 RCTs with 1695 adults – there were

no paediatric studies (Fig. 1 and Table 1) [16–21, 28,

72 © 2014 The Association of Anaesthetists of Great Britain and Ireland

Anaesthesia 2015, 70, 71–83 Albrecht et al. | Dexamethasone for peripheral nerve blocks

35–56]. Authors of 11 RCTs provided additional data

[16, 17, 19–21, 45, 50, 51, 54–56]. One RCT did not

report any pre-specified outcome [35] and we were

unable to generate means (SD) from a single RCT

[43].

A number of RCTs were categorised as high risk

or unclear risk for some bias domains (Fig. 2). All but

six studies [20, 35–37, 39, 47] examined brachial

plexus blockade: interscalene [16, 17, 21, 45, 46, 53];

supraclavicular [19, 28, 38, 40–44, 48–50, 52, 54, 55]

or axillary [18, 51, 56]. The injection was placed under

ultrasound guidance [17, 19–21, 36, 37, 45, 46, 48, 50,

54], with a nerve stimulator [16, 18, 40, 42, 49, 51–53,

55] or following anatomical landmarks [28, 35, 38, 39,

41, 43, 44, 47, 56], and was supplemented by general

anaesthesia in seven RCTs [16, 17, 21, 37, 45, 46, 53]

or spinal anaesthesia in one RCT [36]. The adminis-

tered dose of dexamethasone was 4 mg [28, 35, 39, 45,

47, 50, 55], 5 mg [46], 8 mg [17–21, 28, 36–38, 40–44,

48, 49, 51–54, 56] or 10 mg [16]. Local anaesthetics

with short-term [18, 35, 39, 40, 51, 54–56] or med-

ium-term [19] action were injected in nine RCTs,

while 20 RCTs injected local anaesthetics with long-

term action [16, 17, 20, 21, 28, 36–38, 41–50, 52, 53].

With two exceptions [35, 39], RCTs used 10–50 ml of

injectate.

Figure 1 PRISMA flow diagram showing literature search results.


Albrecht et al. | Dexamethasone for peripheral nerve blocks Anaesthesia 2015, 70, 71–83

Table

1Trial

characteristics.

Reference

Group(n)

Localanaesthetic

Surgery

Nerveblock,

tech

nique

Other

anaesthesia

Postoperative

analgesia

Primary

outcome

Aggarw

aletal.

[35]

Dexa

methasone

4mg(24)

Control(24)

Lidocaine2%,1.8

ml+

adrenaline5lg.m

l�1

Dental

Inferioralveolar,

landmark

None

Nodetail

Rate

of

anaesthesia

Akkaya

etal.

[36]

Dexa

methasone

8mg(21)

Control(21)

Levo

bupivacaine0.25%

,30ml

Caesarean

section

TAP,US

Spinal

IVtramadol

Durationof

analgesia

Ammarand

Mahmoud[37]

Dexa

methasone

8mg(30)

Control(30)

Bupivacaine0.25%

,20ml

Open

hysterectomy

TAP,US

General

Paracetamol

IVPCA

morphine

Pain

on

move

ment

Bais

etal.[38]

Dexa

methasone

8mg(25)

Control(25)

Ropivacaine0.5%

,30ml

Hand

Forearm

Elbow

Supraclavicu

lar,

landmark

None

Nodetail

Nodetail

Bhargava

etal.

[39]

Dexa

methasone

4mg(20)

Control(20)

Lidocaine2%,1.8

ml+

adrenaline5lg

.ml�

1Dental

Pterygomandibular,

landmark

None

Ibuprofen

Nodetail

Biradaretal.

[40]

Dexa

methasone

8mg(30)

Control(30)

Lidocaine1.5%,27ml+

adrenaline5lg

.ml�

1Hand

Forearm

Elbow

Supraclavicu

lar,

AC

None

IMdiclofenac

IVmorphine

Onsetof

sensory

blockade

Cummings

etal.[17]

Dexa

methasone

8mg(103)

Control(106)

Bupivacaine0.5%

,30mlor

ropivacaine0.5%

Shoulder

Interscalene,

AC�

US

General

Paracetamol

Oxyco

done

IVmorphine

Durationof

analgesia

Daretal.[41]

Dexa

methasone

8mg(40)

Control(40)

Ropivacaine0.5%

,30ml

Hand

Forearm

Elbow

Supraclavicu

lar,

landmark

None

IMdiclofenac

Nodetail

Desm

etetal.

[16]

Dexa

methasone

10mg(49)

Control(46)

Ropivacaine0.5%

,30ml

Shoulder

Interscalene,AC

General

Paracetamol

IVdiclofenac

IMpiritramide

Durationof

analgesia

Ganvitetal.

[42]

Dexa

methasone

8mg(30)

Control(30)

Ropivacaine0.5%

,30ml

Hand

Forearm

Elbow

Supraclavicu

lar,

AC

None

IMdiclofenac

Nodetail

Golw

ala

etal.

[43]

Dexa

methasone

8mg(30)

Control(30)

Lidocaine2%,15ml+

bupivacaine0.5%

,15ml+

epinephrine5lg

.ml�

1

Forearm

Elbow

Supraclavicu

lar,

landmark

None

IVdiclofenac

Nodetail

Islam

etal.[44]

Dexa

methasone

8mg(30)

Control(30)

Lidocaine2%,15ml+

bupivacaine0.5%

,15ml

Hand

Forearm

Elbow

Supraclavicu

lar,

landmark

None

Nodetail

Nodetail

Kawanishi

etal.[45]

Dexa

methasone

4mg(12)

Control(12)

Ropivacaine0.75%

,20ml

Shoulder

Interscalene,AC

General

IVflurbiprofen

Loxo

profen

Durationof

analgesia

Kim

etal.[46]

Dexa

methasone

5mg(20)

Control(20)

Levo

bupivacaine0.5%,10ml

Shoulder

Interscalene,

US+AC

General

IVketorolac,

IMmorphine

Nodetail



Table

1(con

tinu

ed)

Reference

Group(n)

Localanaesthetic

Surgery

Nerveblock,

tech

nique

Other

anaesthesia

Postoperative

analgesia

Primary

outcome

Mahmoud

etal.[47]

Dexa

methasone

4mg(23)

Control(25)

Bupivacaine0.5%

,10ml

Posterioreye

Peribulbar,

landmark

None

Paracetamol,

IVpethidine

Durationofblock

Mova

fegh

etal.[18]

Dexa

methasone

8mg(20)

Control(20)

Lidocaine1.5%,34ml

Hand

Forearm

Axillary,AC

None

Nodetail

Durationof

sensory

blockade

Parrington

etal.[19]

Dexa

methasone

8mg(24)

Control(21)

Mepivacaine1.5%

,30ml

Hand

Forearm

Supraclavicu

lar,

US

None

IVfentanyl

Paracetamol

Codeine

Oxy

codone

Durationof

analgesia

Pateletal.[48]

Dexa

methasone

8mg(30)

Control(30)

Lidocaine2%

,15ml+

bupivacaine0.5%

,15ml+

adrenaline5lg.m

l�1

Hand

Forearm

Elbow

Supraclavicu

lar,

US

None

IMdiclofenac

Nodetail

Pathaketal.

[49]

Dexa

methasone

8mg(25)

Control(25)

Lidocaine2%

,20ml+

bupivacaine0.5%

,16ml+

adrenaline5lg.m

l�1

Hand

Forearm

Elbow

Supraclavicu

lar,

AC

None

Nodetail

Nodetail

Persecetal.

[50]

Dexa

methasone

4mg(35)

Control(25)

Levo

bupivacaine0.5%

,25ml

Hand

Forearm

Supraclavicu

lar,

AC+US

None

IVdiclofenac

Durationof

analgesia

Rahangdale

etal.[20]

Dexa

methasone

8mg(27)

control(27)

Bupivacaine0.5%

,0.45ml.kg�1+

adrenaline3.3

lg.m

l�1

Ankle

Foot

Sciatic,

US

None

Paracetamol

Hyd

roco

done

Quality

of

reco

very

Saritasand

Sabuncu

[51]

Dexa

methasone

8mg(15)

Control(15)

Prilocaine2%,5ml.kg�1

Hand

Forearm

Axillary,US

None

IMdiclofenac

Nodetail

Shaikhetal.

[52]

Dexa

methasone

8mg(27)

control(27)

Bupivacaine0.25%

,38ml

Hand

Forearm

Elbow

Supraclavicu

lar,

AC

None

IMdiclofenac

Nodetail

Shresthaetal.

[28]

Dexa

methasone

4–8

mg(20)

Control(20)

Lidocaine2%

,20–2

5ml+

bupivacaine0.5%

,20–2

5ml+

adrenaline5lg.m

l�1

Hand

Forearm

Supraclavicu

lar,

landmark

None

Nodetail

Nodetail

Tandocetal.

[53]

Dexa

methasone

8mg(30)

Control(28)

Bupivacaine0.5%

,40ml+

epinephrine5lg.m

l�1

Shoulder

Interscalene,AC

General

Paracetamol

Ibuprofen

Hyd

roco

done

Durationof

analgesia

Trabelsietal.

[54]

Dexa

methasone

8mg(20)

Control(20)

Lidocaine2%

,15ml

Hand

Forearm

Elbow

Supraclavicu

lar,

US

None

IVparacetamol

SCmorphine

Durationof

analgesia

Vieiraetal.

[21]

Dexa

methasone

8mg(44)

Control(44)

Bupivacaine0.5%

,20ml+

adrenaline5lg.m

l�1+

clonidine75mg

Shoulder

Interscalene,US

General

Hyd

roco

done

Oxy

codone

Hyd

romorphone

Durationof

analgesia



Table

1(con

tinu

ed)

Reference

Group(n)

Localanaesthetic

Surgery

Nerveblock,

tech

nique

Other

anaesthesia

Postoperative

analgesia

Primary

outcome

Yadavetal.

[55]

Dexa

methasone

4mg(30)

Control(30)

Lidocaine1.5%,24ml+

adrenaline5lg

.ml�

1Hand

Forearm

Supraclavicu

lar,

AC

None

IMdiclofenac

Nodetail

Yaghoobietal.

[56]

Dexa

methasone

8mg(21)

Control(19)

Lidocaine1%,40ml

Forearm

Axillary,

landmark

None

IVpethidine

Durationof

analgesia

AC,alternatingcurrentnervestim

ulation;

GA,generalanaesthesia;

IM,intram

uscular;IV

,intravenou

s;PCA,patient-controlledanalgesia;

SC,subcutaneous;TAP,transver-

susabdo

minisplane;US,

ultrasou

nd.

Figure 2 Cochrane collaboration’s risk of bias sum-mary: evaluation of risk of bias items for each includedstudy. Green circle, low risk of bias; red circle, highrisk of bias; yellow circle, unclear risk of bias.



Dexamethasone shortened the onset of sensory

blockade (Fig. 3) and motor blockade (Fig. 4). Dexa-

methasone prolonged the duration of analgesia or sen-

sory block (Fig. 5, random-effects model). With a

fixed-effect model, dexamethasone increased the mean

(95% CI) duration of analgesia by 136 (127–145) min,

when injected with local anaesthetics with short- or

medium-term action, p < 0.00001, and by 406

(400–413) min when injected with local anaesthetics

with long-term action, p < 0.00001. The funnel plot

(Fig. 6) was asymmetric with a regression line inter-

cept (95% CI) of 11.14 (9.53–12.75), p < 0.00001. Dur-

ing the meta-regression analysis, one study was

excluded as the authors used doses of 4 and 8 mg

indiscriminately [28]. There was no association

between the total dose of perineural dexamethasone

and the mean increase in duration of analgesia:

r2 = 0.02, p = 0.54. This was confirmed by subgroup

analysis, in which the mean (95% CI) durations of

analgesia with 4 mg and 8 mg dexamethasone were

not different with local anaesthetics of short- or

medium-term action (200 (51–350) min vs 251 (175–

327) min, respectively, p = 0.55) or long-term action

(461 (240–682) min vs 480 (403–557) min, respec-

tively, p = 0.88). Dexamethasone prolonged motor

blockade (Fig. 7). The relative rate (95% CI) of block

failure was not significant, 0.72 (0.43–1.20), p = 0.21.

Table 2 presents secondary outcomes of the effect of

perineural dexamethasone on postoperative pain. Peri-

neural dexamethasone reduced the rate of postopera-

tive nausea and vomiting (Fig. 8).

One RCT reported a single case of superficial

wound infection treated by local incision and drainage

and also reported that dexamethasone increased mean

(SD) serum glucose concentrations by 3.8

(1.2) mg.dl�1. Seven RCTs recorded the rate of neuro-

logical complications [16, 17, 19, 28, 40, 53, 55]: one of

286 participants who had perineural dexamethasone

reported symptoms, with persistent paraesthesia related

to cervical disc herniation [16]. No other complications

related to perineural dexamethasone were reported.

DiscussionWe found that perineural dexamethasone prolonged

the durations of analgesia and motor blockade from

short-, medium- and long-term action local anaesthet-

ics. Similarly, dexamethasone was associated with a

reduction in pain scores at rest during the intermediate

(8–12 h) and late (24 h) postoperative periods and in

movement at all times. At 24 postoperative hours,

cumulative morphine consumption and the rate of

nausea or vomiting were also reduced. Dexamethasone

slightly reduced the onset times of sensory and motor

blockades, which we think is clinically unimportant.

Figure 3 Effect of perineural dexamethasone on the onset time of sensory blockade. LA, local anaesthetics.



Figure 4 Effect of perineural dexamethasone on the onset time of motor blockade. LA, local anaesthetics.

Figure 5 Effect of perineural dexamethasone on duration of analgesia according to type of local anaesthetics used.LA, local anaesthetics.



Although inconsistently reported, neither neurological

complications nor infections were described, while a

single study found increased blood glucose concentra-

tions after dexamethasone administration [16]. Our

evaluation of the relationship between the dose of

dexamethasone and duration of analgesia was incon-

clusive. We did not find evidence that a dexametha-

sone dose of 4 mg was less effective than 8 or 10 mg,

which most RCTs administered without justification.

Dose-finding studies are needed to define better the

optimal balance between dose, effects and side-effects,

particularly at doses lower than 4 mg.

Fewer than 300 participants were monitored for

neurological complications, so we cannot conclude that

dexamethasone has no effect. Cummings et al.

calculated that 16 000 patients would be required to

demonstrate a doubling of the baseline complication

rate of 0.4% [17]. Although caution is warranted, ani-

mal studies have provided encouraging results, con-

cluding that neurological injury is absent [7, 14, 57].

During in-vitro studies, Ma et al. demonstrated a

potential protective effect of dexamethasone against

local anaesthetic-induced cell injury [58] and a series

of 2000 intrathecal injections of 8 mg dexamethasone

for the treatment of post-traumatic visual disturbance

in 200 patients failed to demonstrate any neurological

sequelae [59]. Nevertheless, clinicians must be aware

that perineural dexamethasone represents off-label use

and solutions free of neurotoxic preservatives should

be used [60, 61]. Finally, although the safety profile of

perineural dexamethasone is promising, it should be

noted that intravenous dexamethasone at a dose of

0.1–0.2 mg.kg�1 could have a comparable analgesic

effect [16, 20, 62] and could obviate the need for peri-

neural injection. Further comparative evaluation of

these routes for administration is warranted.

This meta-analysis is limited by the absence of

systematic definitions for certain endpoints, such as

duration of analgesia. Although we acknowledge that

duration of analgesia, duration of sensory blockade

and time to first analgesic request are not synony-

mous, they are surrogate markers of a meaningful

clinical concept of a pain-free period after surgery.

–20 –10 0 10 200

1

2

3

4

5

6

Standard difference in means

Prec

isio

n (1

/SE

)

Figure 6 Funnel plot of the effect of perineural dexa-methasone on duration of analgesia.

Figure 7 Effect of perineural dexamethasone on the duration of motor blockade. LA, local anaesthetics.



Table 2 Secondary outcomes after perineural dexamethasone injection.

Outcome RCT

Group

Mean difference (95% CI) I2 (%) p value

Dexamethasone Control

Mean SD n Mean SD n

Morphine consumption*0–2 h [37] 0 0 30 0 0 30 �1 (�2.77 to 0.77) NA 0.27

[19] 0.6 2.2 24 1.6 3.6 218–12 h [37] 3.1 2.4 30 16.6 12.8 30 �7.8 (�20.87 to 5.27) 78 0.24

[19] 10.5 25.3 24 10.3 12.3 2124 h [37] 4.1 3.3 30 19.2 11.9 30 �7.93 (�15.55 to �0.32) 90 0.04

[19] 10.3 27 24 9 15.3 21[20] 10.1 8.5 27 11.6 4.9 27[21] 3.1 4.6 44 15.9 11.5 44

Rest VAS0–2 h [46] 5 2 20 10 2 20 �2.55 (�5.54 to 0.44) 83 0.09

[50] 10 4 35 12 4 25[54] 15.5 6.9 20 15 5.1 20

8–12 h [46] 3 3 20 26 5 20 �19.80 (�29.02 to �10.58) 84 < 0.0001[19] 28 29 24 57 30 21[50] 10 8 35 22 13 25

24 h [39] 20 7.2 20 32 7.6 20 �19.94 (�27.50 to �12.38) 88 < 0.00001[17] 30 37 52 50 35 54[17] 40 30 51 50 30 52[45] 22.5 20.1 12 42.5 28.3 12[46] 24 6 20 37 6 20[19] 37 33 24 38 27 21[50] 10 10 35 26 12 25[20] 14 28 27 40 36 27[54] 24 14.7 20 74 13.5 20[21] 30 25 44 59 22 44

Movement VAS0–2 h [37] 4.9 1.3 30 28.1 11.1 30 �28.60 (�43.97 to �13.22) 61 0.0003

[20] 0 30 27 40 44 278–12 h [37] 15.7 3.1 30 25.4 8 30 �9.70 (�12.77 to �6.63) NA < 0.0000124 h [37] 22.3 5.5 30 24.1 6.4 30 �13.72 (�25.45 to �1.98) 87 0.02

[17] 40 30 52 55 20 54[17] 50 25 51 70 20 52[20] 21 34 27 44 35 27

Patient satisfaction [19] 96 10 24 98 10 21 4.46 (�4.27 to 13.18) 89 0.32[20] 98 4 27 97 7 27[21] 95 15 44 80 15 44

RCT, randomised controlled trial; VAS, visual analogue scale.*Intravenous equivalent dose (mg).

Figure 8 Effect of perineural dexamethasone on the rate of postoperative nausea and vomiting. LA, localanaesthetics.



The asymmetry of the funnel plot, along with a sig-

nificant Egger’s test, indicate the presence of small

studies effects, possible causes of which include publi-

cation bias, selective outcome reporting or poor

methodological design. Another limitation is the vari-

ability in anaesthetic strategies employed in the

included studies. For example, peripheral nerve blocks

were combined with general anaesthesia in about 25%

of the articles. The method of nerve location varied

(anatomical landmarks, nerve stimulator or ultra-

sound-guided), as did the volume of local anaesthetics

and the addition of other perineural adjuncts, such as

adrenaline [20, 28, 35, 39, 40, 43, 48, 49, 53, 55] or

adrenaline and clonidine [21]. Each of these factors

may contribute to the substantial heterogeneity

observed in the primary outcome. All RCTs blocked

the brachial plexus, with six exceptions [20, 35–37,

39, 47]. We are therefore unable to draw conclusions

regarding the potential efficacy of perineural dexa-

methasone in other peripheral nerve blocks, such as

those in the distribution of the lumbar or sciatic

plexus, and further research in this area is warranted.

Finally, a number of pre-defined endpoints could not

be assessed, as the required data were not captured

by the included trials.

In summary, perineural dexamethasone at a dose

of 4 mg prolongs the duration of analgesia after local

anaesthetic peripheral nerve blockade with efficacy

similar to a dose of 8 mg and without any reported

serious adverse effects. Dexamethasone is an efficacious

adjunct to local anaesthetics, but clinicians should be

aware that dose-ranging studies are needed.

AcknowledgementsWe are grateful to Mrs Isabelle von Kaenel for the

assistance in the literature search. Dr Albrecht has

received grants from the Swiss Academy for Anaesthe-

sia Research (SACAR), Lausanne, Switzerland.

Competing interestsNo external funding or competing interests declared.

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