Eur J Anaesthesiol 2015; 32:751758

ORIGINAL ARTICLE

Combination of dexamethasone and local anaesthetic

solution in peripheral nerve blocks
A meta-analysis of randomised controlled trials
Thi Mum Huynh, Emmanuel Marret and Francis Bonnet
BACKGROUND Dexamethasone decreases postoperative
pain and prolongs the duration of local anaesthetic peripheral
nerve blocks in studies including a limited number of patients.
OBJECTIVE The objective of this study is to evaluate the
effect of combining dexamethasone with local anaesthetic on
sensory and motor peripheral nerve blockade in adults.
DESIGN A systematic review with meta-analysis of randomised controlled trials.
DATA SOURCES We systematically searched in Medline,
Embase, Google Scholar and Cochrane Controlled Trials
Register up to December 2013.
ELIGIBILITY CRITERIA Randomised trials testing dexamethasone combined with local anaesthetic.
RESULTS Twelve trials (1054 patients, 512 receiving perineural dexamethasone) were included. Ten studies evaluated dexamethasone for brachial plexus nerve block. Four
to 10 mg dexamethasone-containing local anaesthetic
solutions had a faster onset of action and resulted in a

significant increase in the duration of analgesia [weighted

mean difference (WMD) 351 min, 95% confidence interval
(95% CI) 288 to 413, P < 0.001] and motor blockade (WMD
277 min, 95% CI 167 to 387, P < 0.001) compared with
local anaesthetic solutions alone. Time to onset of sensory
and motor blocks was significantly reduced with dexamethasone (WMD
78 s, 95% CI
112 to
44, and
90 s, 95%
CI
131 to
48, respectively). Dexamethasone significantly
decreased postoperative nausea and vomiting (PONV, 9 vs.
27%, relative risk 0.36, 95% CI 0.19 to 0.70). Subgroup
analyses showed that dexamethasone approximately
doubled the duration of postoperative analgesia when it
was combined with intermediate-acting (lidocaine, mepivacaine) or long-acting (bupivacaine, ropivacaine) local anaesthetics.
CONCLUSION Combining dexamethasone with local
anaesthetics results in a prolongation of the duration of
peripheral nerve block.
Published online 13 March 2015

Introduction
Dexamethasone is commonly used in anaesthesia to
prevent postoperative nausea and vomiting (PONV).1
Two recent meta-analyses have documented that dexamethasone also reduced postoperative pain and opioid
requirement.2,3 Intravenous dexamethasone has also
been shown to improve postoperative pain control in
patients receiving spinal or epidural morphine.4 Hong
et al.5 reported that intravenous dexamethasone in combination with a caudal block with ropivacaine prolonged
the duration of postoperative analgesia without adverse
effects in children undergoing orchidopexy. Experimentally, dexamethasone combined with local anaesthetic
may also reinforce peripheral nerve block. In animals,

bupivacaine-dexamethasone microspheres prolonged the

duration of rat sciatic nerve or sheep intercostal nerve
blocks.6,7 In healthy volunteers, dexamethasone combined with bupivacaine in microspheres also prolonged
the duration of analgesia after peripheral nerve block.8,9
In agreement with these results, several studies performed in a small series of patients have found an increase
in the duration of sensory blockade when dexamethasone
was used in combination with local anaesthetic in peripheral nerve blocks.
Consequently, we sought to perform a meta-analysis of
the published randomised trials assessing the clinical

From the Department of Anaesthesiology and Intensive Care, Tenon Hospital, Assistance Publique Hopitaux de Paris, Pierre and Marie Curie University, Paris, France
Correspondence to Dr Emmanuel Marret, MD, PhD, France American Hospital of Paris, 63 Bd Victor Hugo, 9220 Neuilly-sur-Seine, France
E-mail: drmarret@gmail.com
0265-0215 Copyright 2015 European Society of Anaesthesiology. All rights reserved.

DOI:10.1097/EJA.0000000000000248

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

752 Huynh et al.

effect of combining dexamethasone with local anaesthetic on sensory and motor blockade, onset time and
side effects for peripheral nerve blocks performed
in adults.

Materials and methods

This meta-analysis is reported according to PRISMA
recommendations for meta-analysis. A protocol for this
study was not registered.
A wide search strategy was used to retrieve relevant
reports in Embase, Medline, Cinhal, Biosis, Central
and Google Scholar. The searching terms dexamethasone, nerve block, local anaesthetic, lidocaine or
lignocaine, mepivacaine, bupivacaine, ropivacaine,
levobupivacaine, chloroprocaine, articaine, prilocaine and adjuvants were combined. Additional articles
were retrieved through hyperlinks and by manually
searching reference lists in original published articles,
review articles and correspondence. We completed our
research by consulting abstracts, published or not, presented at the American Society of Anesthesiologists,
European Society of Anaesthesiology and Societe Francaise dAnesthesie-Reanimation meetings from 2000
to 2012.
The last electronic research was in December 2013.
There was no language restriction. Authors were contacted for additional information on methods and results
when required.
The following inclusion criteria were applied: randomised treatment allocation; comparison of dexamethasone
added to a local anaesthetic (experimental intervention)
with the same local anaesthetic regimen without dexamethasone (control intervention); peripheral singleinjection nerve or plexus block; and adults undergoing
surgery. When other adjuvants were added to local
anaesthetic (for instance epinephrine), the data were
considered if the comparison was strictly controlled
(i.e. both experimental and control groups received the
same regimen excepted for dexamethasone).
Exclusion criteria were continuous local anaesthetic
administration or repeated injection; intravenous regional
anaesthesia (Biers block); dexamethasone administered
only intravenously; local anaesthetics used in microspheres; healthy volunteers; children (younger than 18
years); and animal studies. To overcome random play of
chance on estimation of treatment effects, we excluded
studies with fewer than 10 participants per group.
The primary evaluation criterion was the duration of
analgesia defined as the delay before the first request
for analgesics. Other endpoints were duration of motor
blockade and onset time of sensory and motor blockades,
postoperative pain scores at 24 and 48 h, PONV and
dexamethasone-related side effects such as infection,
neurological complications or haematoma.

One author (T.H.) extracted relevant information from

original reports. A second author (E.M.) checked all
extracted data. Discrepancies were resolved by discussion with the third author (F.B.). When continuous data
were not reported as mean  SD, we computed them
whenever feasible. Quality of data reporting was assessed
using the Cochrane Collaborations tool for assessing risk
of bias in randomised trials evaluating selection, performance, detection, attrition and reporting bias. The risk of
bias was classified as low risk, high risk or unclear risk
according to the recommendations of Higgins et al.10
Each article was also scored using the Oxford Modified
Scale, an eight-point (0 to 7) scale evaluating randomisation, blinding and completeness of patient follow-up.
The lowest possible score was 1.11
Statistical analysis

When not reported in the article, we considered that an

intention-to treat analysis was performed on the original
data. For continuous data, mean differences with 95%
confidence interval (95% CI) were first calculated for
each individual study. A weighted mean difference
(WMD) was computed to summarise the overall effect.
A random effects model was used when the test for
heterogeneity was significant (P < 0.10). To explore
the effect of dexamethasone in different settings (subgroup analyses), we compared the degree of efficacy of
dexamethasone in combination with intermediate and
long-acting local anaesthetics. For dichotomous endpoints, the Mantel-Haenszel like procedure for relative
risk (RR) was used to pool RRs of individual studies. For
all pooled RRs reaching statistical significance, we computed the number needed to treat (NNT) as the inverse
of the difference of the proportion of patients who had
any event in the dexamethasone group and the control
group. CIs of the NNT were constructed by inverting and
exchanging the limits of the 95% CI for the RR. The
NNT and 95% CI were calculated with the internetbased program Visual Rx (http://www.nntonline.net/).
Analyses were performed using Review Manager (Computer program, version 5.1.6; The Nordic Cochrane
Center, The Cochrane Collaboration, Copenhagen, Denmark, 2011).

Results
Of 1568 retrieved titles, 17 were potentially relevant
(Fig. 1). We excluded five studies. One was performed
in healthy volunteers. The second study evaluated
chronic pain. Three abstracts were excluded because
of missing relevant information. We eventually analysed
data from 12 randomised trials including 13 comparisons
(1054 patients, 512 receiving dexamethasone).
Ten studies evaluated dexamethasone in brachial plexus
nerve blocks (five supraclavicular block, four interscalene
block and one axillary block)1221 and two in other
peripheral nerve blocks (perineal block and transversus

Eur J Anaesthesiol 2015; 32:751758

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

Dexamethasone and peripheral nerve block 753

Fig. 1

Embase

Medline

Cinhal

Biosis

Central

Google
scholar

ASA/SFAR
abstracts

1568 hits
Inadequate reference (n = 1551)
Potentially relevant RCTs (n = 17)
Healthy volunteers (n = 1)
Chronic pain (n = 1)
Lack of information (n = 3)
Valid RCTs (1054 patients, 512 received perineural dexamethasone) (n = 12)

Bupivacaine
(n = 6)

Ropivacaine
(n = 2)

Lidocaine
(n = 3)

Mepivacaine
(n = 1)

Lidocaine +
Bupivacaine
(n = 1)

Flowchart of process selection. RCT, randomised controlled trial; n, number of manuscripts. One trial had four arms: bupivacaine and placebo,
bupivacaine and dexamethasone, ropivacaine and placebo, ropivacaine and dexamethasone.

abdominis plane block).22,23 All the nerve blocks were

performed as a single injection in patients undergoing
upper limb surgery (10 trials, four performed in patients
scheduled for shoulder surgery), haemorrhoidectomy or
abdominal hysterectomy. General anaesthesia was combined with regional anaesthesia in seven trials (shoulder
surgery, haemorrhoidectomy and hysterectomy).
Dexamethasone was combined with intermediate-acting
local anaesthetic [lidocaine alone (three studies), mepivacaine (one study)] or long-acting local anaesthetics
[ropivacaine (two studies), bupivacaine (six studies),
combination of lidocaine and bupivacaine (one study)].
Eleven trials evaluated a single dose of dexamethasone
(8 mg in nine studies; 10 or 4 mg in one study each). One
trial compared two doses of dexamethasone (8 vs. 4 mg).
Two trials had three arms comparing intravenous dexamethasone, perineural dexamethasone and placebo
(Table 1). Dexamethasone was compared with tramadol
in one trial and with epinephrine in another.19,21 Some
patients had a failed block and data were not reported for
some outcomes.
The procedure of randomisation was adequately described
in 10 trials (83%). Concealment of treatment allocation was
described in 10 trials (83%) (Table 2). Nine studies were
double-blinded (75%). Follow-up was completed in 11
trials. The median quality score was six (range 2 to 7).
Duration of postoperative analgesia

Duration of analgesia, defined as the time before the first

analgesic administration, was reported in all studies

(n 874 patients; Fig. 2). All comparisons were significantly in favour of dexamethasone. In controls, the
median time to first postoperative analgesic administration was 325 min (range 98 to 888 min). Dexamethasone significantly increased the duration of analgesia to
about 351 min (95% CI 288 to 413, P < 0.001). This result
remained statistically significant when only studies using
upper extremity nerve blocks were pooled (WMD
420 min, 95% CI 326 to 511, P < 0.001).
Duration of motor blockade

Duration of motor blockade was reported in five

trials.12,15,17,18,21 Four comparisons were significantly in
favour of dexamethasone, and the difference was not
significant in one trial. In controls, the median duration
of motor blockade was 202 min (range 130 to 1500 min).
Dexamethasone significantly increased the duration of
motor blockade (WMD 278 min, 95% CI 168 to 389,
P < 0.001) (Fig. 3).
Subgroup analyses

Subgroup analyses were performed to test the impact of

adding dexamethasone to intermediate-acting (four trials,
n 207) and long-acting (eight trials, n 667) local anaesthetics (Fig. 2). Median duration of analgesia in the control
groups was 167 min (range 98 to 228 min) with intermediate-acting local anaesthetic solutions and 708 min (range
162 to 888 min) with long-acting local anaesthetic
solutions. Dexamethasone approximately doubled
(Fig. 2) the duration of postoperative analgesia in combination with all tested local anaesthetic solutions. Similarly,
dexamethasone increased the duration of motor block of

Eur J Anaesthesiol 2015; 32:751758

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754 Huynh et al.

Table 1

Characteristics of clinical trials included in the meta-analysis

Number of Quality
patients
scorea Nerve block

Author
Abdelmonem
and Rizk23

60

2/1/2/1

Dose of
dexamethasone Local anaesthetics

Perianal

8 mg

Ammar and
Mahmoud22

60

2/1/3/1

Transversus
8 mg
abdominis plane

Biradar et al.12

60

2/0/3/1

Supraclavicular

8 mg

Cummings et al.14

218

2/1/3/1

Interscalene

8 mg

Desmet et al.13

150

2/1/3/1

Interscalene

10 mg

Golwala et al.20

60

1/0/0/1

Supraclavicular

8 mg

Movafegh et al.15

60

2/1/3/0

Axillary

8 mg

Parrington et al.16

58

2/1/3/1

Supraclavicular

8 mg

Shrestha et al.21

60

2/1/3/1

Supraclavicular

8 mg

Tandoc et al.17

90

2/1/3/1

Interscalene

4 and 8 mg

Vieira et al.18

88

2/1/3/1

Interscalene

8 mg

Yadav et al.19

90

1/1/2/1

Supraclavicular

4 mg

(1) Bupivacaine 100 mg and perineural dexamethasone 8 mg (20)

(2) Bupivacaine 100 mg and 0.9% saline (20)
(3) Bupivacaine 100 mg and intravenous dexamethasone 8 mg (20)
(1) Bupivacaine 50 mg and dexamethasone 8 mg (30)
(2) Bupivacaine 50 mg and saline (30)
(1) Lidocaine 1.5% (7 ml kg
1), epinephrine 1 : 200 000 and dexamethasone
8 mg (30)
(2) Lidocaine1.5% (7 ml kg
1), epinephrine 1 : 200 000 and 0.9% saline (30)
(1) Ropivacaine 150 mg and dexamethasone 8 mg (54)
(2) Ropivacaine 150 mg and 0.9% saline (54)
(3) Bupivacaine 150 mg and dexamethasone 8 mg (54)
(4) Bupivacaine 150 mg and 0.9% saline (56)
(1) Ropivacaine 150 mg and perineural dexamethasone10 mg (50)
(2) Ropivacaine 150 mg and intravenous dexamethasone 10 mg (50)
(3) Ropivacaine 150 mg and 0.9% saline (50)
(1) Lidocaine 300 mg, bupivacaine 75 mg and epinephrine 1 : 200 000
dexamethasone 8 mg (30)
(2) Lidocaine 300 mg, bupivacaine 75 mg and epinephrine1 : 200 000
0.9% saline (30)
(1) Lidocaine 510 mg and dexamethasone 8 mg (30)
(2) Lidocaine 510 mg and 0.9% saline (30)
(1) Mepivacaine 450 mg and dexamethasone 8 mg (30)
(2) Mepivacaine 450 mg and saline (28)
(1) Bupivacaine 0.5% 2 mg kg
1 and tramadol 2 mg kg
1 (30)
(2) Bupivacaine 0.5% 2 mg kg
1 and dexamethasone 8 mg (30)
(1) Bupivacaine 200 mg, epinephrine 1 : 200 000 and dexamethasone
8 mg (30)
(2) Bupivacaine 200 mg, epinephrine 1 : 200 000 and 0.9% saline (30)
(3) Bupivacaine 200 mg, epinephrine 1 : 200 000 and dexamethasone
4 mg (30)
(1) Bupivacaine 100 mg, epinephrine 1 : 200 000 and clonidine 75 mg
dexamethasone 8 mg (44)
(2) Bupivacaine 100 mg, epinephrine 1 : 200 000 and clonidine 75 mg
0.9% saline (44)
(1) Lidocaine 360 mg and dexamethasone 4 mg (30)
(2) Lidocaine 360 mg and epinephrine 1 : 200 000 (30)
(3) Lidocaine 360 mg and neostigmine 500 mg (30)

Oxford Modified Scale: randomisation (0 to 2)/concealment of treatment allocation (0 to 1)/blinding (0 to 3)/description of withdrawals (0 to 1).

intermediate and long-acting local anaesthetics (Fig. 3).

Pain intensity at 24 h after surgery was reported in three
trials14,16,22 (n 366) evaluating dexamethasone combined with long-acting local anaesthetics. The median
Table 2

pain score at 24 h was 55 (range 24 to 70). Dexamethasone-containing solutions decreased visual analogue scale
(VAS) scores compared with plain local anaesthetic
solutions (WMD
16.05, 95% CI
30.19 to
1.91).

Risk of bias and methodological quality assessment of included trials

Abdelmonem and Rizk23

Ammar and Mahmoud22
Biradar et al.12
Cummings et al.14
Desmet et al.13
Golwala et al.20
Movafegh et al.15
Parrington et al.16
Shrestha et al.21
Tandoc et al.17
Vieira et al.18
Yadav et al.19

Randomisation

Concealment of
allocation

Blinding
patient

Blinding provider of
the intervention

Blinding
observer

Follow-up

, low risk of bias; ?, unclear.

Eur J Anaesthesiol 2015; 32:751758

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Dexamethasone and peripheral nerve block 755

Fig. 2

Experimental
Control
Study or subgroup
Mean
SD Total Mean
SD Total Weight
Duration of analgesia with intermediate-acting LAs
Biradar
326
58.6
29
159
20.1
29
9.4%
Movafegh
242
76
24
98
33
20
9.2%
Parrington
332
17
24
228
41
21
9.4%
Yadav
454.2 110.7
30 176.5
53.5
30
9.1%
Subtotal (95% CI)
107
100 37.1%
Heterogeneity: Tau2 = 3411.69; Chi2 = 56.85, df= 3 (P < 0.00001); I2 = 95%
Test for overall effect: Z = 5.64 (P < 0.00001)
Duration of analgesia with long-acting LAs
Abdelmonem
21
18 162.3
16.9
19
287.7
9.5%
75.3
30 325.4
63.6
30
Ammar
459.8
9.2%
Cummings Bupivacaine
54
888 280.21
52
6.8%
1344 391.4
Cummings Ropivacaine
52
51
6.5%
1332 476.46
708 182.36
1433
Desmet
4.2%
619
49
824
510
46
265
30
300
88.8
30
Golwala
900
7.6%
30 453.17
72.81
30
8.4%
Shrestha
1028.17 194.51
30
28
4.6%
Tandoc
530
780
240
1500
1457
434
44
833
267
44
6.1%
Vieira
Subtotal (95% CI)
337
330 62.9%
Heterogeneity: Tau2 = 41253.75; Chi2 = 367.40, df= 8 (P < 0.00001); I2 = 98%
Test for overall effect: Z = 6.77 (P < 0.00001)
Total (95% CI)
444
430 100.0%
Heterogeneity: Tau2 = 10756.57; Chi2 = 425.58, df= 12 (P < 0.00001); I2 = 97%
Test for overall effect: Z = 10.97 (P < 0.00001)
Test for subgroup differences: Chi2 = 16.25, df= 1 (P < 0.0001); I2 = 93.8%

Mean difference
IV, Random, 95% CI

Mean difference
IV, Random, 95% CI

167.00 [144.45, 189.55]

144.00 [110.33, 177.67]
104.00 [85.19, 122.81]
277.70 [233.70, 321.70]
170.74 [111.45, 230.03]

125.40 [113.08, 137.72]

134.40 [99.13, 169.67]
456.00 [326.78, 585.22]
624.00 [485.16, 762.84]
609.00 [381.49, 836.51]
600.00 [499.99, 700.01]
575.00 [500.68, 649.32]
720.00 [510.55, 929.45]
624.00 [473.44, 774.56]
483.13 [343.31, 622.95]

350.58 [287.94, 413.22]

500 250 0
250 500
Favours control Favours dexamethasone

Meta-analysis of the duration of postoperative analgesia (min). Subgroup analysis comparing the efficacy of dexamethasone added to intermediateacting and long-acting local anaesthetics. Duration of postoperative analgesia was defined as time until the first analgesic request. Meta-analyses
were performed using a random effect model. Symbols and horizontal lines are mean differences (single trials) or WMDs (combined data) with 95%
CIs. CI, confidence interval; IV, inverse variance; LA, local anaesthetic; SD, standard deviation; WMD, weighted mean difference.

Other outcomes

The time to onset of sensory blockade was documented

in seven trials (n 356; (Supplemental Data File,
http://links.lww.com/EJA/A67)).12,15,16,19 21,23 Six comparisons were significantly in favour of dexamethasone.

In controls, median time to onset of sensory blockade

was 10 min (range 4.6 to 18.5 min). Dexamethasone
significantly shortened onset time when studies
were pooled (WMD
78 s, 95% CI
112 to
44,
P < 0.001).

Fig. 3
Control
Experimental
Study or subgroup
Mean
SD Total Mean
SD Total Weight
3.1.1 Duration of motor block with intermediate-acting LAs
Biradar
290.6 52.7
29
29 32.9%
135.5
20.3
24
8.4%
310
817
20
130
31
Movafegh
53
49 41.3%
Subtotal (95% CI)

Mean difference
IV, Random, 95% CI

Mean difference
IV, Random, 95% CI

155.10 [134.55, 175.65]

180.00 [147.14, 507.14]
155.20 [134.68, 175.71]

Heterogeneity: Tau2 = 0.00; Chi2 = 0.02, df= 1 (P = 0.88); I2 = 0%

Test for overall effect: Z = 14.83 (P < 0.00001)
3.1.2 Duration of motor block with long-acting LAs
393.03 98.96
30 202.93 30.55
Shrestha
30 32.1%
30
28
1.8%
900
2340 2040
1500
Tandoc
44
44 24.8%
292
827
239
1374
Vieira
102 58.7%
Subtotal (95% CI)
104
Heterogeneity: Tau2 = 62907.82; Chi2 = 37.69, df= 2 (P < 0.00001); I2 = 95%
Test for overall effect: Z = 2.51 (P < 0.01)
Total (95% CI)
157
151 100.0%
Heterogeneity: Tau2 = 9425.35; Chi2 = 49.61, df= 4 (P < 0.00001); I2 = 92%
Test for overall effect: Z = 4.96 (P < 0.00001)
Test for subgroup differences: Chi2 = 2.52, df= 1 (P < 0.11); I2 = 60.3%

190.10 [153.04, 227.16]

840.00 [37.49, 1642.51]
547.00 [435.51, 658.49]
423.06 [93.00, 753.12]

277.7 [167.92, 387.56]

500 250
0
250 500
Favours experimental Favours control

Meta-analysis of the duration of motor block (min). Subgroup analysis comparing the efficacy of dexamethasone added to intermediate-acting and
long-acting local anaesthetics. Meta-analyses were performed using a random effect model. Symbols and horizontal lines are mean differences
(single trials) or WMDs (combined data) with 95% CIs. CI, confidence interval; IV, inverse variance; LA, local anaesthetic; SD, standard deviation;
WMD, weighted mean difference.

Eur J Anaesthesiol 2015; 32:751758

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756 Huynh et al.

Time to onset of motor blockade was described in seven

trials (n 356).12,15,16,1921,23 Four comparisons were
significantly in favour of dexamethasone; the difference
was not significant in three trials. In controls, the median
time to onset of motor blockade was 8 min (range 5.4
to 22). Dexamethasone significantly shortened this time
duration (WMD
90 s, 95% CI
131 to
49, P < 0.001;
P < 0.001 for test of heterogeneity).
Postoperative pain scores were reported in seven trials
but at different times. Pain scores measured by VAS
graded from 0 to 100 were evaluated at 24 h in four trials
(403 patients). Decrease in pain intensity did not reach
statistical significance (WMD
13, 95% CI
25 to 0.4,
P 0.06).14,16,18,22 At 48 h, there was no difference (three
trials, WMD
3, 95% CI
9 to 2).14,18,22
PONV were reported in four trials.16,20,22,23 Dexamethasone significantly decreased the incidence of PONV (9 vs.
27%, RR 0.36, 95% CI 0.19 to 0.70, P 0.003; P 0.88 for
test of heterogeneity, NNT 6, 95% CI 5 to 13).
Incomplete block, or block failure, defined as a need for
additional intravenous sedative or analgesic medication,
additional nerve block or wound infiltration during
surgery were reported in five trials.14,16,18,20,23 In controls,
the risk of incomplete block was 7.7% with local anaesthetic alone and 5.9% with dexamethasone, a difference
that was not statistically significant (RR 0.77, 95% CI 0.43
to 1.38, P 0.38; P 0.95 for test of heterogeneity). No
adverse effects of dexamethasone were reported. A
neurological complication was described in one trial.
One patient in the dexamethasone group complained
of hypoaesthesia after interscalene block.13 Exploration
revealed spinal disc herniation. No haematoma was
reported.

Discussion
This meta-analysis of 12 randomised controlled trials
documents that the combination of dexamethasone with
local anaesthetic solutions in peripheral nerve blocks
prolongs the durations of analgesia and motor blockade.
These effects were documented with both intermediate
and long-acting local anaesthetics. In addition, perineural
administration of dexamethasone decreased the incidence of PONV.
This meta-analysis included 512 patients who had
received perineural dexamethasone. Upper limb blocks
were performed in most of the studies. All the studies
demonstrated separately and collectively the superiority
of dexamethasone-containing local anaesthetic solutions
over plain solutions in terms of durations of analgesia and
motor blockade. As the quality of most of the studies was
adequate, supported by an Oxford Modified Score value
of more than 5, the results of this meta-analysis can be
considered to have a low risk of bias. Three doses of
dexamethasone were studied (4, 8 and 10 mg), making
the results more heterogeneous. However, no dose effect

could be evaluated. Only one study by Tandocet et al.17

compared 4 and 8 mg of dexamethasone combined with
bupivacaine. No difference was found between the two
groups. The minimal effective dose of dexamethasone is
also unknown. The definition of the duration of sensory
blockade was the same in all the studies. It was considered as the delay between local anaesthetic administration and the first analgesic administration. This time
accounts for the duration of analgesia, which is not,
strictly speaking, the duration of the anaesthetic blockade. The aim of the administration of an adjuvant to a
local anaesthetic solution is either to prolong anaesthesia
or to prolong analgesia induced by local anaesthetic, or
both. In the case of dexamethasone, the mean gain in the
duration of analgesia is more than 6 h, which compares
favourably with the prolongation achieved with other
adjuvants such as neostigmine or clonidine.19,24 Unfortunately, the duration of motor blockade is also dramatically
increased, which makes it less easy to manage in patients
scheduled for ambulatory surgery or when a rapid recovery of motor function is required. In addition, in some
patients, an extremely long duration of motor blockade
could increase nerve block complications, necessitating
prolonged monitoring until recovery of motor function,
and increasing anxiety of patients. Finally, the benefit of
adding dexamethasone to local analgesia with infiltration
may be interesting to investigate for cases in which motor
block may be problematic.9
The mechanism of action of dexamethasone is not documented. A drawback of the studies designs is that a third
arm corresponding to intravenous administration of dexamethasone was included in only two trials.13,23 A comparable increase in the duration of analgesia was
documented by the perineural and intravenous routes
of administration in these two trials. In addition, intravenous dexamethasone increases the duration of analgesia after caudal block with ropivacaine in children.5 It is
consequently difficult to consider that the local effect of
dexamethasone is stronger than the systemic one, and
this point needs to be clarified.
No drug-related adverse effects, especially peripheral
neuropathy, were reported in patients who received
dexamethasone-containing local anaesthetic solution.
However, the number of patients is not sufficient to
permit definitive conclusions to be reached regarding
the lack of neurotoxicity of dexamethasone. Epidemiological studies suggest that complications after regional
anaesthesia affect about one in 8000 patients.25,26 These
complications are drug-specific, and dose and timedependent.27
The safety of dexamethasone is controversial. In isolated
nerve cells (dorsal root ganglia), Williams et al.28 found
that ropivacaine-induced neurotoxicity was increased by
large doses of dexamethasone (time and concentrationdependent). The mechanisms include an increase in the

Eur J Anaesthesiol 2015; 32:751758

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

Dexamethasone and peripheral nerve block 757

intracellular calcium flow (inducing cell apoptosis) and

activation of induced apoptosis factors and caspase 3.
Some studies have shown that dexamethasone activated
apoptosis genes coding for the mRNA of tumour necrosis
factor (TNF) a and b, and interleukin-1.29 Tissue injury
depends on the injection site. After intrafascicular neural
injection, direct injury to myelin and axons has been
induced by hydrocortisone and triamcinolone. Similar
injuries have been observed with dexamethasone, but
to a lesser extent. Eventually, the neurotoxicity of dexamethasone may depend on the solvent associated with
the active agent (propylene glycol).30
This meta-analysis has several limitations. First, peripheral nerve blocks were not ultrasound-guided in most
cases. Second, the volume of injection was usually more
than 20 ml. Utrasonography is now used commonly in
regional anaesthesia and may increase the efficacy and
the reliability of blocks. The benefit of dexamethasone
needs further investigation when small volumes of local
anaesthetic are used. Third, the current meta-analysis
does not allow determination of whether perineural
administration of dexamethasone is more effective than
intravenous administration to prolong the duration of
peripheral nerve blocks. Fourth, two trials included in
the meta-analysis were not strictly controlled.19,21
Dexamethasone was compared with two other adjuvants (tramadol, epinephrine). However, the duration
of postoperative analgesia was longer with dexamethasone. Fifth, only positive trials have been published.
The possibility of publication bias cannot be ruled
out completely.
All trials included in this meta-analysis were positive with
regard to the duration of postoperative analgesia with
dexamethasone. Small doses of perineural dexamethasone, that is less than 4 mg, were not studied. The dose
response effect of adding dexamethasone to local anaesthetics remains unclear and needs further investigation.
Others adjuvants such as a2-agonists prolong the duration
of postoperative analgesia after peripheral nerve block
but increase the risk of hypotension, fainting or sedation.24 Multimodal analgesia is frequently used for relieving postoperative pain. It combines several analgesics to
provide equivalent or better analgesia with reduced
analgesic side effects. This concept may be tested in
the context of peripheral nerve block. High doses of
dexamethasone increase the neurotoxicity induced by
ropivacaine.28 Small doses of adjuvants (dexamethasone,
clonidine) added to small volumes and/or low concentrations of local anaesthetics for nerve blocks need evaluation.

Conclusion
This meta-analysis supports a significant prolongation of
the peripheral nerve block by combining dexamethasone
with local anaesthetic solution. Questions remain concerning the mechanism of action, the optimal dose, the

lack of toxicity and the comparison with intravenous

administration.

Acknowledgements relating to this article

Assistance with the study: none.
Funding and sponsorship: this work was funded by departmental
resources only. This work should be attributed to Department of
Anaesthesiology and Intensive Care, Tenon Hospital, Assistance
Publique Hpitaux de Paris, Pierre and Marie Curie University,
Paris VI.
Conflicts of interest: none.
Presentation: this work was presented in part at the September 2012
annual meeting of the French Society of Anaesthesiology and
Intensive Care (SFAR) in Paris, France.

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