British Journal of Anaesthesia 110 (6): 91525 (2013)

Advance Access publication 15 April 2013 . doi:10.1093/bja/aet066

Facilitatory effects of perineural dexmedetomidine

on neuraxial and peripheral nerve block: a systematic
review and meta-analysis
F. W. Abdallah 1 and R. Brull 2*
1

Department of Anesthesia and Pain Management, St Michaels Hospital, and Womens College Hospital, University of Toronto, Toronto,
Canada
2
Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, and Womens College Hospital,
University of Toronto, Toronto, Canada
* Corresponding author: Department of Anesthesia, Toronto Western Hospital, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8.
E-mail: richard.brull@uhn.ca

Dexmedetomidine has
been used to prolong the
duration of local
anaesthetics (LAs).
In this meta-analysis,
nine randomized
controlled trials on
perineural
dexmedetomidine in
neuraxial and peripheral
nerve blocks were
selected.
Dexmedetomidine
prolonged block duration.
More studies are required
to establish the safety of
using dexmedetomidine
as a perineural adjunct to
LAs.

Summary. Nerve blocks improve postoperative analgesia, but their benefits may be shortlived. This quantitative review examines whether perineural dexmedetomidine as a local
anaesthetic (LA) adjuvant for neuraxial and peripheral nerve blocks can prolong the
duration of analgesia compared with LA alone. All randomized controlled trials (RCTs)
comparing the effect of dexmedetomidine as an LA adjuvant to LA alone on neuraxial
and peripheral nerve blocks were reviewed. Sensory block duration, motor block duration,
block onset times, analgesic consumption, time to first analgesic request, and sideeffects were analysed. Results were combined using random-effects modelling. A total of
516 patients were analysed from nine RCTs. Five trials investigated dexmedetomidine as
part of spinal anaesthesia and four as part of a brachial plexus (BP) block. Sensory block
duration was prolonged by 150 min [95% confidence interval (CI): 96, 205, P,0.00001]
with intrathecal dexmedetomidine. Perineural dexmedetomidine used in BP block may
prolong the mean duration of sensory block by 284 min (95% CI: 1, 566, P0.05), but
this difference did not reach statistical significance. Motor block duration and time to first
analgesic request were prolonged for both intrathecal and BP block. Dexmedetomidine
produced reversible bradycardia in 7% of BP block patients, but no effect on the
incidence of hypotension. No patients experienced respiratory depression. Dexmedetomidine
is a potential LA adjuvant that can exhibit a facilitatory effect when administered
intrathecally as part of spinal anaesthesia or peripherally as part of a BP block. However,
there are presently insufficient safety data to support perineural dexmedetomidine use in
the clinical setting.
Keywords: acute pain; regional techniques; anaesthetic techniques; regional; brachial
plexus; analgesic techniques; subarachnoid; analgesics; postoperative; sympathetic
nervous system; dexmedetomidine

Regional anaesthesia techniques provide important advantages compared with general anaesthesia and systemic
analgesia, including excellent pain control, reduced sideeffects, and shortened stay in the post-anaesthesia care
unit.1 3 However, these early advantages can be short-lived3
and limited by the relatively brief duration of action4 5 of currently available local anaesthetics (LAs),6 potentially resulting in block resolution before the period of worst
postoperative pain.7 8 Increasing the volume (dose) of LAs
may prolong the duration of analgesia,9 but may also increase the risk of LA systemic toxicity.10 Although continuous
catheter-based nerve blocks can extend postoperative analgesia,11 12 their placement requires additional time, cost,
and skill.13 While a novel sustained-release encapsulated

(liposomal) preparation of bupivacaine is presently undergoing investigation in phase III trials,14 a variety of perineural
adjuvants,15 including buprenorphine,16 clonidine,17 dexamethasone,18 magnesium,19 and midazolam,20 21 have been
used to prolong the duration of analgesia of nerve blocks
with varying degrees of success. Dexmedetomidine, an a2
adrenoreceptor agonist,22 was first proposed as an adjuvant
capable of prolonging duration of sensory and motor block
produced by nerve blocks by Memis and colleagues.23
However, the series of clinical trials that followed produced
contradictory results.24 27 Some trials have shown that perineural dexmedetomidine reduces the onset time and prolongs the duration of sensory and motor block.23 25 26
Conversely, other trials have demonstrated either a delay in

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Editors key points

BJA

Abdallah and Brull

sensory and motor block onset time27 or no effect on sensory

and motor block duration24 with the use of perineural dexmedetomidine. The primary objective of this quantitative
review is to determine whether the administration of perineural dexmedetomidine as an LA adjuvant for neuraxial

and peripheral nerve blocks can prolong the duration of analgesia compared with LA alone.

Methods
The PRISMA28 recommendations were followed in the preparation of this manuscript.

Eligibility criteria
Table 1 Trial characteristics. Dex, dexmedetomidine; n, number of
trials
Author/year

Quantity (n)

Percentage

Source database
Medline

44.4

Google scholar

22.2

Hand search

22.2

Grey literature

11.1

Listed in Index Medicus

44.4

Not listed in Index Medicus

55.5

Trial source country

Egypt

22.2

India

33.3

Jordan

11.1

Lebanon

11.1

Turkey

22.2

Jadad score
5 (excellent quality)

66.6

33.3

1 (poor quality)

Number of subjects
,50

11.1

50 100

88.8

Adult (18)

100

Paediatric (,18)

Age

Gender
Female

Male

11.1

Both

88.8

Outcomes assessed
Analgesia

100

Block characteristics

100

Dex side-effects

100

Location of surgery
Abdominal

22.2

Extremity, upper

44.4

Extremity, lower

22.2

Combination

11.1

Disposition

916

Inpatient

33.3

Outpatient

22.2

Both

22.2

Unspecified

22.2

Literature search
We retrieved RCTs from the US National Library of Medicine
database, MEDLINE; the Excerpta Medica database, Embase;
Cochrane Database of Systematic Reviews; and Cochrane
Central Register of Controlled Trials databases (January
1985 August 2012). The search terms dexmedetomidine
and medetomidine were used in combination with the
search terms perineural, adjuvant, adjunct, and admixture.
Searches were combined using the Boolean operator AND
with medical subject headings analgesia/pain relief/pain
control/pain prevention/and pain management and the
medical subject headings regional anaesthesia/nerve block/
block/neuraxial block/central block/peripheral block. The
search was limited to trials published in the English language. We also reviewed the reference lists of selected
trials for additional RCTs. Trials that are unpublished or in progress were not included.

Data collection and presentation

The two authors (F.W.A. and R.B.) independently evaluated
the methodological quality of the included trials using the
Jadad score;45 and a final score was designated by consensus for each RCT. We selected sensory block duration as the
primary endpoint, while motor block duration, sensory and
motor block onset time, analgesic consumption, time to
first analgesic request, pain scores,46 and dexmedetomidinerelated adverse effects (hypotension, bradycardia, respiratory
depression, and postoperative sedation)47 48 were defined as
secondary endpoints. The authors each used a standardized

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Trial source journal

We sought to identify all randomized controlled trials (RCTs)

that examined the effects of adding perineural dexmedetomidine to LA (dexmedetomidine group) compared with LA
alone (control group) on neuraxial or peripheral nerve block
characteristics, postoperative analgesia, and dexmedetomidine-related side-effects in surgical patients undergoing
regional anaesthesia. Blocks performed for either anaesthesia or postoperative analgesia were included. RCTs were
excluded if dexmedetomidine was used as a stand-alone
perineural agent without LA,29 or administered via a nonperineural route,23 24 30 38 if continuous nerve blocks were
performed,39 40 and if blocks were performed in paediatric
patients where block characteristics could not be
assessed.41 44 Only trials that explicitly mentioned obtaining
approval from the local ethics committee or institutional
review board were considered. The use of dexmedetomidine
as part of i.v. regional anaesthesia (Bier block) was not considered for the purposes of this review.

BJA

Perineural dexmedetomidine

data sheet to extract and record trial results, which were

compared and any differences were resolved by reexamination of the source trials.

Meta-analysis

Results
We retrieved 37 articles, of which nine met our inclusion criteria.25 27 51 56 Tables 1 and 2 present the trial characteristics and outcomes assessed for each trial, respectively. The
methodological quality45 of all nine trials was good; six
trials26 51 52 54 56 achieved a Jadad score of 5 out of 5,
while the remaining three25 27 53 achieved a score of 4 out
of 5. The countries of origin for all eight trials were Middle
Eastern; all protocols were approved by the local ethics committee or institutional review board of their respective institution. Figure 1 summarizes the search results, including
the RCTs retrieved, excluded, and presently reviewed.
Twenty-eight trials were excluded because of the interventions examined (n14), populations studied (n7), active
comparators (n5), study design (n1), and language of
publication (n1) (Appendix). The trials reviewed included
a total of 516 patients for analysis; 274 patients in the dexmedetomidine group and 242 in the control group. Five
trials examined the effect of neuraxial dexmedetomidine
administered intrathecally as part of spinal anaesthesia,26
51 52 54 57
and four assessed peripheral dexmedetomidine
administered as part of a brachial plexus (BP) block.25 27 55 56
All nine trials reviewed herein used a long-acting LA,
namely ropivacaine,53 bupivacaine,26 27 51 52 54 56 and levobupivacaine (Table 1).25 55 We did not identify any RCTs
that investigated the use of peripheral dexmedetomidine
for truncal or lower extremity blocks, or neuraxial dexmedetomidine in epidural or caudal blocks. Two trials included two
dexmedetomidine groups51 52 (low dose and high dose).

Sensory block duration

Data regarding sensory block duration were available from all
trials reviewed and are presented in Figure 2. Intrathecal administration of dexmedetomidine as part of spinal

Block characteristics
When used intrathecally, dexmedetomidine hastened sensory
block onset by 2 min (95% CI: 22.96, 20.11, P0.04) or 19%,
prolonged motor block duration by 132 min (95% CI: 87.69,
176.74, P0.00001) or 88%, and delayed the time to first analgesic request by 293 min (95% CI: 174.32, 411.41,
P0.00001) or 127% compared with LA alone. The motor
block onset time was similar between the dexmedetomidine
and control groups (Table 3).
Administering perineural dexmedetomidine as part of a
BP block resulted in a prolongation of motor block duration
by 268 min (95% CI: 15.47, 520.06, P0.04) or 87%, and
an increase in time to first analgesic request by 345 min
(95% CI: 102.68, 587.23, P0.005) or 70% compared with
LAs alone. The sensory and motor block onset times were
similar between the dexmedetomidine and control groups
(Table 3).

Dexmedetomidine-related adverse effects

Because of the diversity in the definitions of dexmedetomidine-related adverse effects in the reviewed trials, the
results of these outcomes are reported as standardized
units. The incidence of hypotension was similar between
the dexmedetomidine and the control groups (Table 3). The
incidence of bradycardia was higher in patients who received
dexmedetomidine as part of a BP block (7% vs 0%, P0.03),
but there was no difference with intrathecal administration.
The observed bradycardia was transient, successfully
reversed by i.v. atropine administration, and did not recur
later during the postoperative period.
Respiratory depression was explicitly assessed in four
trials.25 27 52 55 None of the patients in these trials experienced respiratory depression.
The incidence of postoperative sedation was evaluated in
four trials26 51 53 that examined the intrathecal administration of dexmedetomidine; a six-point measurement scale
was used in two of the trials51 52 and a four-point scale
was used in the other two trials.26 53 The heterogeneity of
scales used and the inconsistency in reporting rates of occurrence precluded any quantitative analyses. Qualitatively, one
trial52 reported higher sedation levels in a group of patients
receiving high-dose intrathecal dexmedetomidine (15 mg)
without specifying the actual rate of occurrence, while

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Data entry was performed by one author (F.W.A.) and

rechecked by another (R.B.). Meta-analytic techniques
(Revman 5.1, Cochrane Library, Oxford, UK) were used to
pool data whenever possible. Data from trials with more
than two intervention groups receiving different doses of
dexmedetomidine via the same route were combined into
a single group as recommended by the Cochrane Handbook.49 Dichotomous and continuous outcomes were analysed using random-effects modelling. The odds ratio (OR)
and 95% confidence intervals (CIs) are reported for dichotomous outcomes, while the standardized mean difference
and 95% CI are reported for continuous outcomes. Differences were considered statistically significant when the
95% CI did not include 1 for OR and 0 for the standardized
mean difference. Heterogeneity of the pooled results was
assessed using the I 2 statistic.50

anaesthesia prolonged the mean sensory block duration by

150 min (95% CI: 95.94, 204.75, P,0.00001), which is a relative increase of 72% compared with LAs alone. The heterogeneity among the pooled studies in this subgroup was
significant (I 2 0.95; P,0.00001).
The data signal that peripheral dexmedetomidine used in
a BP block at the axillary,25 55 supraclavicular,27 and infraclavicular56 levels may prolong the mean duration of sensory
block by 284 min (95% CI: 1.39, 565.68, P0.05), a relative
increase of 76% compared with LAs alone, but this difference
did not reach statistical significance. Heterogeneity among
trials in this subgroup was also high (I 2 1; P,0.00001).

Study

Jadad Surgery
score

Block/
use

Kanazi and
colleagues26

TURBT,
TURP

Spinal/ 60
surgical

Al-Mustafa
and
colleagues51

TURBT,
TURP, TVT

Spinal/ 66
surgical

Eid and
colleagues52

ACL

Spinal/ 48
surgical

Gupta and
colleagues53

Groups (n)

Local
anaesthetic

Adjuvant

BJA

Primary Block characteristics

Analgesic outcomes
Dex-related adverse effects
outcome Sensory Sensory Motor Motor
Postop Time to
Analgesic
Hypotension Bradycardia Postop Respiratory
block
block
block block
pain
first
consumption
sedation depression
onset
duration onset duration
analgesic
time
time
request

Neuraxial
Intrathecal

Lower
extremity

Spinal/ 60
surgical

(1) Dex+
bupivacaine
(16)
(2) Clonidine+
bupivacaine
(16)
(3) Bupivacaine
(19)

(1) Dex 5 mg+

bupivacaine
(21)
(2) Dex 10 mg+
bupivacaine
(21)
(3) NS+
bupivacaine
(22)

(1) Dex 10 mg+

bupivacaine
(15)
(2) Dex 15 mg+
bupivacaine
(16)
(3) NS+
bupivacaine
(16)

Sensory
block
duration

12.5 mg of 0.5%
isobaric
(1) Dex 5 mg
bupivacaine
(2) Dex 10 mg
(3) NS

Sensory
block
duration

3 ml of 0.5%
hyperbaric
bupivacaine

Sensory
block
duration

Time to

first
analgesic
request

3 ml of 0.75%
ropivacaine

(1) Dex 10 mg
(2) Dex 15 mg
(3) NS

(1) Dex 5 mg
(2) NS

Abdallah and Brull

(1) Dex+
ropivacaine
(30)
(2) NS+
ropivacaine
(30)

12 mg of 0.75%
hyperbaric
(1) Dex 3 mg
bupivacaine
(2) Clonidine
(3) None

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918

Table 2 Trial outcomes. ACL, anterior cruciate ligament repair; AXB, axillary nerve block; Dex, dexmedetomidine; ICB, infraclavicular block; Intraop, intraoperative; N/D, not defined; NS, normal
saline; Postop, postoperative; SCB, supraclavicular block; TURBT, transurethral resection of bladder tumour; TURP, transurethral resection of prostate tumour; TVT, tension-free vaginal tape

Abdominal, Spinal/ 90
lower
surgical
(1) Dex+
extremity
bupivacaine
(30)
(2) Magnesium+
bupivacaine
(30)
(3) NS+
bupivacaine
(30)

2 ml of 0.75%
hyperbaric
bupivacaine

Forearm,
hand

AXB/
60
surgical

40 ml of 0.5%
levobupivacaine

Forearm,
hand

SCB/
75
surgical

Forearm,
hand

AXB/
64
surgical

Forearm,
hand

ICB/
60
surgical

Time to

first
analgesic
request

N/D

(1) Dex 10 mg
(2) Magnesium
(3) NS

Perineural dexmedetomidine

Shukla and
colleagues54

Peripheral
Brachial plexus
Esmaoglu
and
colleagues25

Gandhi and
colleagues27

Kaygusuz55

Ammar and 5
Mahmoud56

(1) Dex+
levobupivacaine
(30)
(2) NS+
levobupivacaine
(30)

(1) Dex+
bupivacaine
(35)
(2) NS+
bupivacaine
(35)

(1) Dex+
levobupivacaine
(30)
(2) NS+
levobupivacaine
(30)

(1) Dex+
bupivacaine
(30)
(2) NS+
bupivacaine
(30)

38 ml 0.25%
bupivacaine

39 ml 0.5%
levobupivacaine

30 ml 0.33%
bupivacaine

Motor
block
(1) Dex 100 mg in duration
1 ml
(2) NS 1 ml

N/D
(1) Dex 30 mg in
2 ml
(2) NS 2 ml

Sensory
block
(1) Dex 1 mg kg21 duration
in 1 ml
(2) NS 1 ml

(1) Dex 0.75 mg

kg21 in 1 ml
(2) NS 1 ml

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BJA

Abdallah and Brull

Dexmedetomidine OR
Medetomidine

Analgesia OR
Pain Relief OR
Pain Control OR
Pain Prevention OR
Pain Management

37 Records identified
through other sources

AND

Perineural OR
Adjuvant OR
Adjunct OR
Admixture

AND

Regional Anaesthesia OR
Nerve Block OR
Block OR
Neuraxial Block OR
Central Block OR
Peripheral Block

three trials26 51 53 reported no difference in sedation between

the patients who received intrathecal dexmedetomidine as
an adjunct to spinal anaesthesia and those who did not.
We could not quantitatively analyse our remaining secondary endpoints (pain scores, analgesic consumption) due
to inconsistent reporting and heterogeneous assessment
protocols within and between the source trials. Qualitatively,
these results favour the dexmedetomidine group and are
presented in Table 4.

Discussion

144 Records

139 Records after

removing duplicates

139 Records
screened

102 Excluded records

37 Articles assessed

28 Excluded articles
(Appendix)

9 Trials included

Fig 1 Flowchart summarizing retrieved, included, and excluded

RCTs.

Dex
Study or Subgroup
Neuraxial-intrathecal
Kanazi 200626
Al-Mustafa 200951
Eid 201152
Gupta 201153
Shukla 201154
Subtotal (95% CI)

Mean [Min]
303
283
365.78
468.3
352

SD

[Min]

Total

75
66.65
79.76
36.8
45

16
42
31
30
30
149

Control
Mean [Min]
SD [Min]
190
165.5
238
239.3
194

Total Weight

Mean difference
I.V. random, 95% CI [Min]

48
32.9
57
16.8
55

19
22
16
30
30
117

11.0%
11.1%
11.0%
11.2%
11.1%
55.5%

113.00 [70.38, 155.62]

117.50 [93.10, 141.90]
127.78 [88.18, 167.38]
229.00 [214.52, 243.48]
158.00 [132.57, 183.43]
150.35 [95.94, 204.75]

73.77
36.4
61.7
15.2

30
35
30
30
125

11.1%
11.2%
11.1%
11.2%
44.5%

214.00 [178.52, 249.48]

585.90 [565.70, 606.10]
259.53 [223.87, 295.19]
74.70 [67.21, 82.19]
283.54 [1.39, 565.68]

242 100.0%

208.98 [93.51, 324.44]

Mean difference
I.V. random, 95% CI [Min]

Heterogeneity: 2 = 3607.38; 2 = 88.02, df = 4 (P<0.00001); l 2 = 95%

Test for overall effect: Z = 5.42 (P < 0.00001)
Peripheral-brachial plexus
887
Esmaoglu 201025
732.4
Gandhi 201227
924.15
Kaygusuz 201255
197.4
Ammar 201256
Subtotal (95% CI)

66.23
48.9
78.27
14.4

30
673
35
146.5
30
664.62
30
122.7
125
2
2
2
Heterogeneity: = 82697.47; = 2223.07, df = 3 (P<0.00001); l = 100%
Test for overall effect: Z = 1.97 (P = 0.05)
274
Total (95% CI)
Heterogeneity: 2 = 31010.66; 2 = 2348.66, df = 8 (P<0.00001); l 2 = 100%
Test for overall effect: Z = 3.55 (P = 0.0004)
Test for subgroup differences: 2 = 0.83, df = 1 (P < 0.36); l 2 = 0%

500 250

250

500

Favours control Favours Dex

Fig 2 Forest plot showing sensory block duration. The sample size, mean, standard deviations, and the pooled estimates of the mean
difference are shown. The 95% CIs are shown as lines for individual studies and as diamonds for pooled estimates.

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Our review of the literature suggests that the use of dexmedetomidine as a perineural adjuvant can prolong the durations of both sensory and motor block produced by
long-acting LAs in spinal blocks. For BP blocks, perineural
dexmedetomidine can prolong the duration of motor block;
however, the trend towards prolonged sensory block did
not reach statistical significance. Dexmedetomidine also
hastens the onset of sensory block in spinal anaesthesia
and prolongs the time to first analgesic request in the
setting of both spinal anaesthesia and BP block. The advantages of dexmedetomidine may be offset by an increased
likelihood of transient, reversible bradycardia, and the prolongation of motor block when it is undesirable.
In the context of perineural adjuvants, the efficacy of dexmedetomidine appears to be comparable with buprenorphine16 and dexamethasone18 58 59 when administered
peripherally, and exceeds that of clonidine, magnesium,
and midazolam for both intrathecal19 20 26 54 60 and peripheral17 21 61 applications. However, unlike clonidine, another
a2 adrenoreceptor agonist shown capable of prolonging the

107 Records

BJA

Perineural dexmedetomidine

Table 3 Quantitative results. N/A, not applicable

Studies
included

Dex
mean or
n/N

Control
mean or
n/N

Odds ratio or weighed

mean (95% confidence
interval)

P-value for
statistical
significance

P-value for
heterogeneity

I 2 test for
heterogeneity

Sensory block
onset (min)

26 51 54

5.53

6.82

21.54 (22.96, 20.11)

0.04

0.00001

90%

Motor block onset

(min)

26 51 54

9.33

13.15

24.52 (29.17, 0.13)

0.06

0.00001

95%

Motor block
duration (min)

26 51 52 54

294.46

156.45

132.22 (87.69, 176.74)

0.00001

0.00001

93%

Time to first
analgesic request
(min)

52 53

525.68

231.37

292.87 (174.32, 411.41)

0.00001

0.0003

92%

Incidence of
hypotension (n/N)

26 51 54

9/156

8/118

0.73 (0.20, 2.71)

0.64

0.26

25%

Incidence of
bradycardia (n/N)

26 51 54

3/156

2/118

0.97 (0.04, 21.49)

0.98

0.11

60%

Sensory block
onset (min)

25 27 55 56

13.19

14.89

21.9 (25.08, 1.28)

0.24

0.00001

97%

Motor block onset

(min)

25 27 55 56

12.58

14.15

21.67 (24.93, 1.58)

0.31

0.00001

97%

Motor block
duration (min)

25 27 55 56

600.72

321.20

267.76 (15.47, 520.06)

0.04

0.00001

100%

Time to first
analgesic request
(min)

25 27 55 56

850.97

500.21

344.95 (102.68, 587.23)

0.005

0.00001

99%

Incidence of
hypotension (n/N)

25 27 55 56

2/127

0/127

5.30 (0.25, 114.47)

0.29

N/A

N/A

Incidence of
bradycardia (n/N)

25 27 55 56

9/127

0/127

10.52 (1.27, 87.08)

0.03

0.54

0%

Block type/outcome

Neuraxial
Intrathecal

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Peripheral
Brachial plexus

Table 4 Qualitative results. +, favours Dex; , no difference; Dex, dexmedetomidine; VAS, visual analogue scale
Study

Postoperative
pain

Analgesic
consumption

Comments

Eid and
colleagues52

Dex reduces rest VAS pain scores at 8, 12, 24 h (P,0.05). Dex reduces dynamic
VAS pain scores at 4, 8, 12, 24 h (P,0.05). Dex reduces i.v. diclofenac
consumption by 45% at 24 h; Dex 77.4 mg, control 140.6 mg (P,0.05)

Gupta and
colleagues53

Dex reduces maximum VAS pain scores during first 24 h by 35%; Dex 4.4, control
6.8 (P,0.001). Dex reduces i.m. diclofenac consumption by 64% at 24 h; Dex
72.8 mg, control 202.5 mg (P,0.001)

Dex reduces rest VAS pain scores at 1, 2, 12, 24, 36, 48 h (P,0.05). Dex reduces
i.v. morphine consumption by 64% at 48 h; Dex 4.9 mg, control 13.6 mg
(P0.005)

Neuraxial
Intrathecal
Kanazi and
colleagues26
Al-Mustafa and
colleagues51

Peripheral
Brachial plexus
Ammar and
Mahmoud56

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922

when doses as high as 6.1 mg kg21 were administered via an

epidural route in rabbits.93 While the doses used in the trials
reviewed herein did not exceed 0.2 mg kg21 for intrathecal
and 1 mg kg21 for peripheral administration, the hazards of
drawing conclusions of safety based on isolated small
animal data are self-evident.15 Finally, none of the reviewed
trials justified the safety and compatibility of their dexmedetomidine LA mixture for peripheral and neuraxial use.
In summary, dexmedetomidine is a potential LA adjuvant
that can exhibit a facilitatory effect when administered intrathecally as part of spinal anaesthesia or peripherally as part
of a BP block. However, there are presently insufficient safety
data to support the use of perineural dexmedetomidine in
the clinical setting.

Declaration of interest
None declared.

Funding
This work was supported by departmental funding.

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duration of shorter acting62 64 but not long-acting65 66 LAs,

this review demonstrated that dexmedetomidine clearly prolonged the block duration of long-acting LAs. Also, while clonidine produces preferential extension of sensory block,67 our
review suggests that dexmedetomidine prolongs both
sensory and motor block, a difference that may be disadvantageous by delaying rehabilitation and/or discharge, or
worse, precipitating falls.
The results of our review are subject to several limitations.
The trials included herein were small and characterized by
high levels of heterogeneity, factors that limit the clinical
combinability of the source trials, and the generalizability
of our results. Similarly, the present safety data, however
limited, may not apply to other block types as local neurotoxicity and systemic uptake are both influenced by site-specific
perfusion levels.15 The generalizability of this review is further
limited by publication bias as all source studies originated
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mg52 for the intrathecal route, and 30,27 100 mg,25 0.75,56
or 1 mg kg21 55 for the peripheral route. While these dosing
inconsistencies most likely reflect the absence of human
dose response studies and/or extrapolation from animal
studies,75 82 the variable doses of dexmedetomidine, the different types of LAs used, and the variation between trials in
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have contributed to the statistically significant heterogeneity
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and also time to first analgesic request were achieved even
with the lowest doses of dexmedetomidine, namely, 3 mg
for intrathecal and 30 mg of peripheral administration.
While we could not demonstrate any association between
perineural dexmedetomidine and the frequency of hypotension or respiratory depression, the trials examined herein
were not specifically designed to assess safety. While dexmedetomidine may appear safe in the short term,83 84 systematic preclinical and subsequent human neurotoxicity data,
including the investigation of potential delayed adverse
neurological effects and effects related to prolonged perineural exposure, are lacking.85 Indeed, relevant neurotoxicity
data seem contradictory; while a number of reports suggest
that dexmedetomidine is protective against hypoxicischaemic neuronal injury in rat and human neonatal asphyxia
models,86 92 dexmedetomidine has also been shown to
cause moderate to severe demyelination in white matter

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41

42

43

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46

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49

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Appendix: Excluded trials

Reference
J Med Sci 2008; 8: 660 4

Reason for exclusion

Comparator

Al-Ghanem

Am J Appl Sci 2009; 6: 882 87

Population

Al-Metwalli

Br J Anaesth 2008; 101: 395 9

Intervention

Anand

Indian J Anaesth 2011; 55: 340

Population

Bajwa

Indian J Anaesth 2011; 55: 116 21

Comparator

Bajwa

Saudi J Anaesth 2011; 5: 365 70

Comparator

Cheung

Br J Anaesth 2011; 107: 430 7

Population, intervention

El-Hakim

Acta Anaesthesiol Scand 2010; 54: 703 9

Intervention

El-Hamamsy

Res J Medicine Med Sci 2009; 4: 355 60

Intervention

El-Hennawy

Br J Anaesth 2009; 103: 268 74

Population

Esmaoglu

Eur J Anaesthesiol 2005; 22: 447 51

Intervention

Gupta

J Anaesthesiol Clin Pharmacol 2011; 27: 339

Comparator

Jaakola

J Clin Anesth 1994; 6: 204 11

Intervention

Jain

South Afr J Anaesth 2012; 18: 105 9

Intervention

Kol

Clin Durg Investig 2009; 29: 121 9

Intervention

Memis

Anesth Analg 2004; 98: 835 40

Intervention

Mizrak

J Surg Res 2010; 164: 242 7

Intervention

Mirzak

Middle East J Anesthesiol 2011; 21: 53 60

Intervention

Nasr

Eg J Anaesth 2012; 28: 37 42

Intervention

Obayah

Eur J Anaesthesiol 2010; 27: 280 4

Population

Paswan

Indian J Res 2011; 5: 6 10

Intervention

Paul

Ceylon Med J 2010; 55: 111 5

Intervention

Saadawy

Acta Anaesthesiol Scand 2009; 53: 251 6

Population

Salagado

Rev Assoc Med Bras 2008; 54: 110 5

Language

Schnaider

Rev Bras Anestesiol 2005; 55: 525 31

Design: non-randomized

Sinha

Anaesth Pain Intensive Care 2012; 16: 38 42

Intervention

Neogi

J Anaesthesiol Clin Pharmacol 2010; 26: 149 53

Population

Vieira

Rev Bras Anestesiol 2004; 54: 473 8

Comparator

Handling editor: R. P. Mahajan

925

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First author
Abosedira