REGIONAL ANESTHESIA AND ACUTE PAIN
ORIGINAL ARTICLE
A Multicenter Randomized Comparison Between
Intravenous and Perineural Dexamethasone for
Ultrasound-Guided Infraclavicular Block
Prangmalee Leurcharusmee, MD,* Julian Aliste, MD,† Tom C.R.V. Van Zundert, MD, PhD, EDRA,†
Phatthanaphol Engsusophon, MD,† Vanlapa Arnuntasupakul, MD,‡
Worakamol Tiyaprasertkul, MD,* Amornrat Tangjitbampenbun, MD,‡ Sonia Ah-Kye, MD, FRCPC,†
Roderick J. Finlayson, MD, FRCPC,† and De Q.H. Tran, MD, FRCPC†
Background and Objectives: This multicenter, randomized trial com-
pared intravenous (IV) and perineural (PN) dexamethasone for ultrasound
(US)-guided infraclavicular brachial plexus block. Our research hypothesis
was both modalities would result in similar durations of motor block.
Methods: One hundred fifty patients undergoing upper limb surgery
with US-guided infraclavicular block were randomly allocated to receive
IV or PN dexamethasone (5 mg). The local anesthetic agent (35 mL of
lidocaine 1%-bupivacaine 0.25% with epinephrine 5 μg/mL) was identi-
cal in all subjects. Patients and operators were blinded to the nature of
IV and PN injectates. During the performance of the block, the perfor-
mance time, number of needle passes, procedural pain, and complica-
tions (vascular puncture, paresthesia) were recorded.
Subsequently, a blinded observer assessed the success rate (defined as
a minimal sensorimotor composite score of 14 of 16 points at 30 minutes),
onset time as well as the incidence of surgical anesthesia (defined as the abil-
ity to complete surgery without local infiltration, supplemental blocks, IV
opioids, or general anesthesia). Postoperatively (at 24 hours), the
blinded observer contacted patients with successful blocks to enquire
about the duration of motor block, sensory block, and postoperative
analgesia. The main outcome variable was the duration of motor block.
Results: No intergroup differences were observed in terms of technical
execution (performance time/number of needle passes/procedural pain/
complications), onset time, success rate, and surgical anesthesia. How-
ever, compared to its IV counterpart, PN dexamethasone provided 19%
to 22% longer durations for motor block (15.7 ± 6.2 vs 12.9 ± 5.5 hours;
P = 0.009), sensory block (16.8 ± 4.4 vs 13.9 ± 5.4 hours; P = 0.002),
and postoperative analgesia (22.1 ± 8.5 vs 18.6 ± 6.7 hours; P = 0.014).
Conclusions: Compared with its IV counterpart, PN dexamethasone
(5 mg) provides a longer duration of motor block, sensory block, and post-
operative analgesia for US-guided infraclavicular block. Future dose-finding
studies are required to elucidate the optimal dose of dexamethasone.
(Reg Anesth Pain Med 2016;41: 328–333)
examethasone can prolong the duration of interscalene,1–4
D supraclavicular,5–15 and axillary16,17 brachial plexus blocks.
Postulated mechanisms include inhibition of nociceptive C fibers,
From the *Department of Anesthesia, Maharaj Nakorn Chiang Mai Hospital,
Chiang Mai University, Chiang Mai, Thailand; †Department of Anesthesia,
Montreal General Hospital, McGill University, Montreal, Quebec, Canada;
and ‡Department of Anesthesia, Ramathibodi Hospital, Mahidol University,
Bangkok, Thailand.
Accepted for publication December 13, 2015.
Address correspondence to: De Q.H. Tran, MD, FRCPC, Department of
Anesthesia, Montreal General Hospital, 1650 Ave Cedar, D10-144
Montreal, Quebec, Canada H3G-1A4 (e‐mail: de_tran@hotmail.com).
The authors declare no conflict of interest.
Clinical Trial Registration: Thai Clinical Trails Registry
www.clinicaltrials.in.th Study ID: TCTR20150624001
Copyright © 2016 by American Society of Regional Anesthesia and Pain
Medicine
ISSN: 1098-7339
DOI: 10.1097/AAP.0000000000000386
328 Regional Anesthesia and Pain Medicine • Volume 41, Number 3, May-June 2016
Copyright © 2016 American Society of Regional Anesthesia and Pain Medicine. Unauthorized reproduction of this article is prohibited.
suppression of ectopic neural discharge, peripheral/central anti-
inflammatory effects, and suppression of the neuropeptide immune
response to injury.15 The optimal route of administration remains
controversial. Although some trials report longer analgesia with
perineural (PN) compared to intravenous (IV) dexamethasone,4
other studies have failed to detect significant differences be-
tween the 2 modalities.15,18
In this trial, we set out to compare IV and PN dexamethasone
for ultrasound (US)-guided infraclavicular brachial plexus blocks
(ICBs). As a precautionary measure, we designed the study as
an equivalency trial and hypothesized that both modalities
would result in similar durations. Because analgesic and sensory
duration can be influenced by postoperative pain medications
and trauma to small cutaneous nerves, respectively, we selected
duration of motor block as the primary outcome.
METHODS
The current trial was registered at www.clinicaltrials.in.th
(study ID: TCTR20150624001) on June 24, 2015. After obtaining
ethics committee approval (McGill University Health Center,
Montreal, Quebec, Canada; Maharaj Nakorn Chiang Mai Hospi-
tal, Chiang Mai, Thailand; and Ramathibodi Hospital, Bangkok,
Thailand) and written informed consent, we enrolled 150 patients
undergoing surgery of the forearm, wrist, or hand. Inclusion criteria
were age between 18 and 80 years, American Society of Anesthe-
siologists physical status I to III, and body mass index between
18 and 35 kg/m2. Exclusion criteria were inability to consent to
the study, coagulopathy, sepsis, hepatic or renal failure, allergy to
local anesthetic (LA), preexisting musculocutaneous/median/
radial/ulnar neuropathy, and prior surgery in the infraclavicular fossa.
After arrival in the induction room, an 18- or 20-gauge IV
catheter was placed in the upper limb contralateral to the surgical
site and IV premedication (0.015–0.03 mg/kg of midazolam and
0.6 μg/kg of fentanyl) was administered to patients if necessary.
Supplemental oxygen (nasal cannulae at 4 L/min) and pulse oxim-
etry were applied throughout the procedure.
The ICB was performed according to a previously described
technique.19,20 The 6- to 13-MHz linear US probe (Sonosite
M-Turbo; SonoSite Inc, Bothell, Washington) was applied in a
sterile fashion in the infraclavicular fossa, medially to the coracoid
process, in order to obtain a short axis view of the axillary artery.
A skin wheal was raised with 3 mL of lidocaine 1.0%. Using an in-
plane technique and a cephalad to caudad direction, a 22-gauge,
9-cm block needle (StimuQuick Echo; Arrow International Inc,
Reading, Pennsylvania) was advanced until the tip was located
dorsal to the axillary artery. Thirty-five milliliters of lidocaine
1.0%-bupivacaine 0.25% (obtained by mixing equal parts of lido-
caine 2% and bupivacaine 0.5%) with epinephrine 5 μg/mL was
incrementally injected. All blocks were performed by residents,
fellows, or staff anesthesiologists. Independently of their status,
Regional Anesthesia and Pain Medicine • Volume 41, Number 3, May-June 2016 Dexamethasone for Infraclavicular Block

operators were considered experts if, before the start of the study,
they possessed an experience level equal or superior to 60 ICBs.
Otherwise, they were considered trainees.21
Using a computer-generated sequence of random numbers
and a sealed envelope technique, patients were randomly allocated
to receive IV or PN dexamethasone (5 mg). Randomization was
independently carried out in each of the 3 centers. In the PN
group, 0.5 mL of dexamethasone (10 mg/mL) was administered
with the LA and 0.5 mL of normal saline was injected intravenously.
Conversely, in the IV group, 0.5 mL of normal saline was adminis-
tered with the LA and 0.5 mL of dexamethasone (10 mg/mL) was
injected intravenously. The study solutions were prepared by an
investigator not involved in clinical care so patients and opera-
tors remained blinded to the nature of IV and PN injectates.
For both groups, the imaging time was defined as the time
interval between contact of the US probe with the patient and
the acquisition of a satisfactory picture. The needling time (de-
fined as the temporal interval between the start of the skin wheal
and the end of LA injection through the block needle) was also
recorded. Thus, performance time was defined as the sum of
imaging and needling times. The number of needle passes was
also recorded. The initial needle insertion counted as the first
pass. Any subsequent needle advancement that was preceded
by a retraction of at least 10 mm counted as an additional pass.22
Furthermore, the level of procedural pain (0 = no pain; 10 = worst,
imaginable pain) as well as the incidence of vascular puncture and
paresthesia were recorded.
After LA injection through the block needle, measure-
ments of brachial plexus blockade were carried out every 5 minutes
until 30 minutes by a blinded observer. Sensory blockade of the
musculocutaneous, median, radial, and ulnar nerves was graded
according to a 3-point scale using a cold test: 0 = no block,
1 = analgesia (patient can feel touch, not cold), and 2 = anesthe-
sia (patient cannot feel touch).19,20 Sensory blockade of the
musculocutaneous, median, radial, and ulnar nerves were assessed
on the lateral aspect of the forearm, the volar aspect of the thumb,
the lateral aspect of the dorsum of the hand, and the volar aspect of
the fifth finger, respectively.19,20 Motor blockade was also graded
on a 3-point scale: 0 = no block, 1 = paresis, and 2 = paralysis.19,20
Motor blockade of the musculocutaneous, radial, median, and ul-
nar nerves were evaluated by elbow flexion, thumb abduction,
thumb opposition, and thumb adduction, respectively.19,20 Over-
all, the maximal composite score was 16 points. We considered
the block a success and the patient ready for surgery when a min-
imal composite score of 14 points was achieved, provided the
sensory block score was equal or superior to 7 of 8 points. This
scale has been used in previous studies.19,20 The onset time was
defined as the time required to obtain 14 points. If, after
30 minutes, the composite score was inferior to 14 points,
the patient was transferred to the operating room for the start
of the surgery. For these patients, we did not record an onset
time. Surgical anesthesia was recorded by the same blinded ob-
server and defined as the ability to proceed with surgery without
the need for IV narcotics, general anesthesia, rescue blocks, or LA
infiltration by the surgeon.19,20 However, in case of anxiety (as
voiced by patients or determined by the treating anesthesiolo-
gists), subjects could receive a propofol infusion (25–80 μg/kg
per minute) intraoperatively, provided response to verbal stimulus
was maintained. The blinded observer also recorded the patient's
anthropometric data.

FIGURE 1. CONSORT diagram of patient flow through the study. Onset times could not be recorded for patients with minimal composite
scores inferior to 14 points at 30 minutes. However, the performance time, number of needle passes, procedural pain, operator's experience
level, adverse events (vascular puncture/paresthesia), and surgical anesthesia were recorded for these subjects. BMI, Body mass index.

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Leurcharusmee et al Regional Anesthesia and Pain Medicine • Volume 41, Number 3, May-June 2016

pertaining to technical execution/onset/success/surgical anesthe-

TABLE 1. Patient Characteristics sia were retained for analysis (Fig. 1).
One week after the surgery, patients were contacted by the
IV Dexamethasone PN Dexamethasone
blinded investigator to inquire about complications such as per-
(n = 75) (n = 75) P
sistent numbness/paresthesia or motor deficit.
Age, y 42.5 ± 15.5 45.7 ± 15.1 0.134
Sex (M/F) 49/26 35/40 0.032
BMI, kg/m2 24.4 ± 3.8 24.8 ± 4.4 0.480 Statistical Analysis
ASA physical 56/17/2 44/30/1 0.052
status (I/II/III) In a preliminary pilot study, our experience with PN dexa-
Types of surgery 40/27/6/2 38/24/10/3 0.600 methasone (5 mg) for US-guided ICB revealed a motor block
(hand/wrist/ duration of 802 ± 258.42 minutes. We deemed that a 25% differ-
forearm/elbow) ence in duration (200.5 minutes, ie, 3.3 hours) carries little clinical
significance. Thus, a calculated sample size of 45 patients per
Continuous variables are presented as means ± SD; categorical variables group was required for a statistical power of 0.90 and a type I error
are presented as counts.
of 0.025. Since block duration can only be calculated for success-
ASA indicates American Society of Anesthesiologists; BMI, body ful blocks and because we anticipated a 90% success rate with a
mass index.
35-mL volume,20 50 subjects per group were needed to compen-
sate for block failure. Because the duration of motor block cannot
be accurately measured if the patient cannot be contacted postop-
Postoperatively, patients with successful blocks (minimal eratively or if the block wears off during the patient's sleep, we
composite score of 14 points at 30 minutes) were provided a data elected to recruit an additional 25 subjects per group to account
sheet to record the exact time when they first regained sen- for possible dropout. Thus, a total of 150 patients were enrolled
sation in the fingers (duration of sensory block), moved the across the 3 centers.
fingers (duration of motor block), and experienced pain at the Statistical analysis was performed using SPSS version 21
surgical site (analgesic duration). We did not seek sensation or statistical software (IBM, Armonk, New York). For continuous
movement of specific digits but only of those whose tips were data, normality was first assessed with the Lilliefors test and then
not covered by the cast. The blinded observer contacted study analyzed with the Student t test. Data that did not have a normal
subjects at 24 hours for data collection. In the event that pa- distribution, as well as ordinal data, were analyzed with the
tients could not be reached or that ICBs had receded during Mann–Whitney U test. For categorical data, the χ2 or Fisher
sleep, we did not record any data for the duration of sen- exact test was used. The log-rank test was used to analyze the
sorimotor block and postoperative analgesia. However, data Kaplan–Meier plots for duration of analgesia, sensory, and motor

TABLE 2. Block Performance Data

IV Dexamethasone PN Dexamethasone
(n = 75) (n = 75) P
Imaging time, s 29.2 ± 26.5 37.5 ± 38.2 0.045
Needling time, min 4.5 ± 2.0 4.8 ± 2.3 0.449
Performance time, min 5.0 ± 2.2 5.4 ± 2.5 0.253
Onset time, min 18.0 ± 6.9 17.1 ± 6.3 0.483
Total anesthesia-related time, min 23.1 ± 6.9 22.5 ± 6.7 0.643
Blocks with a minimal composite score of 14 points 65 (86.7) 66 (88.0) >0.999
Surgical anesthesia 71 (94.7) 74 (98.7) 0.367
Operator's experience level (expert/trainee) 24/51 23/52 0.867
No. passes 1 [1–7] 2 [1–5] 0.673
Block-related pain (scale 0–10) 0 [0–7] 1 [0–8] 0.180
Duration of motor block, h; 12.9 ± 5.5 15.7 ± 6.2 0.009
95% CI of the difference of the means –4.9 to −0.72
Duration of sensory block, h; 13.9 ± 5.4 16.8 ± 4.4 0.002
95% CI of the difference of the means –4.58 to −1.06
Duration of postoperative analgesia, h; 18.6 ± 6.7 22.1 ± 8.5 0.014
95% CI of the difference of the means –5.9 to −0.45
Vascular puncture 5 (6.7) 2 (2.7) 0.442
Paresthesia 0 (0.0) 1 (1.3) >0.999
Continuous variables are presented as mean ± SD; categorical variables are presented as count (percentage). Ordinal variables (number of passes and
block-related pain) are presented as median [range].
Total anesthesia-related time is defined as the sum of performance and onset times. Onset and total anesthesia-related times are calculated only for pa-
tients with a minimal composite score of 14 points at 30 minutes.
CI indicates Confidence interval.

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Regional Anesthesia and Pain Medicine • Volume 41, Number 3, May-June 2016 Dexamethasone for Infraclavicular Block

FIGURE 2. Percentage of patients with a minimal composite score of 14 points according to time. Absolute count values are provided inside
each column. Dex, Dexamethasone.

block. All P values presented were 2-sided and values inferior to
0.05 were considered significant.
RESULTS
The 150 subjects were recruited during a period of 3.5 months
(August 2015 to mid-November 2015) (Fig. 1). Sixty-seven, 60,
and 23 patients were enrolled in Montreal, Chiang Mai, and
Bangkok, respectively. A higher male-to-female ratio was present
in the IV group. However, there were no intergroup differences
in terms of age, body mass index, and American Society of Anesthe-
siologists physical status (Table 1). Technical execution (performance
time/number of needle passes/procedural pain/complications) was
comparable between the 2 groups (Table 2).
No intergroup differences were recorded in terms of onset
time, success rate, and surgical anesthesia (Table 2; Fig. 2).
However, compared with its IV counterpart, PN dexametha-
sone provided 19% to 22% longer durations for motor block
(15.7 ± 6.2 vs 12.9 ± 5.5 hours; P = 0.009), sensory block
(16.8 ± 4.4 vs 13.9 ± 5.4 hours; P = 0.002), and postoperative
analgesia (22.1 ± 8.5 vs 18.6 ± 6.7 hours; P = 0.014)
(Table 2; Figs. 3–5).
Patient follow-up at 1 week revealed no sensory or
motor deficit.
DISCUSSION
In this randomized trial, we compared IV and PN dexameth-
asone for US-guided ICB. Our results show that both modali-
ties result in similar onset times and success rates. However, PN
dexamethasone provides longer motor block, sensory block, and
postoperative analgesia. Our findings echo those of Kawanishi
et al4 who observed a longer time to first analgesic request
(P = 0.008) with PN compared to IV dexamethasone for inter-
scalene blocks (with ropivacaine 0.75%). However, our trial con-
tradicts past studies that reported similar block durations for the
2 modalities.15,18,23 We hypothesize that this discrepancy can be
explained by differences in nerve block and LA. Alternately,
similarities between IV and PN dexamethasone may stem from
insufficient statistical power. For instance, in their trial on sciatic

FIGURE 3. Kaplan–Meier survival plot for the duration of motor block. P = 0.020 (log-rank test). Dex, Dexamethasone.

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Leurcharusmee et al Regional Anesthesia and Pain Medicine • Volume 41, Number 3, May-June 2016

FIGURE 4. Kaplan–Meier survival plot for the duration of sensory block. P = 0.012 (log-rank test). Dex, Dexamethasone.

blocks, Rahangdale et al23 observed that PN dexamethasone pro-
longed motor block and time to first analgesia by 5 and 6 hours,
respectively, but these values failed to reach statistical significance.
For interscalene blocks, Desmet et al18 recorded a longer analge-
sic duration with PN compared to IV dexamethasone (1405 vs
1275 minutes). Again the intergroup difference was not statis-
tically significant. Finally, dose constitutes another confound-
ing variable. In our trial, 5 mg was selected because recent
studies suggest PN equivalency between small (4–5 mg) and
large (8–10 mg) doses of dexamethasone.24 However, one cannot
rule out the possibility that high doses could selectively increase
block duration in the IV group thereby achieving parity with
the PN route. For instance, Abdallah et al,15 Desmet et al,18
and Rahangdale et al23 all used doses ≥ 8 mg. In fact, Abdallah
et al15 even observed that, with 8 mg, IV dexamethasone pro-
longed motor blockade to a greater extent than its PN counterpart.
Thus, future dose-finding studies are required to elucidate the
optimal dose of IV (and PN) dexamethasone.
Although statistically significant, the increased durations
in sensorimotor block (2.8–2.9 hours) and postoperative anal-
gesia (3.5 hours) may not seem clinically relevant. Admittedly,
a 2.8-hour-longer motor block falls below the 3.3-hour threshold
used in the sample size justification. However, the increased length
of postoperative analgesia did cross the mark. More importantly,
the longer block duration carries few additional risks because
the ICB technique and dose of dexamethasone remain identical
in both study groups. Thus, the cost–benefit ratio may favor the
PN modality.
The lack of a control group requires discussion. In our
study, all patients received either IV or PN dexamethasone. We
decided to forego enrollment of a purely placebo group (IV and
PN normal saline). We reasoned that, although the optimal method
of administration remains controversial, the literature is replete
with trials demonstrating that patients receiving dexamethasone
fare better than those who do not in terms of onset time, block
duration, postoperative analgesia, or opioid consumption.1–3,5–17
Furthermore, because our standard of practice includes dexametha-
sone (IV or PN), we felt that its non-inclusion would be unethical.
The fact that we only used patients with 14-point minimal
composite scores to tabulate block duration also deserves special
mention. In our trial, 87% to 88% of subjects reached 14 points
(or more) at 30 minutes. In contrast, 95% to 99% of patients
achieved surgical anesthesia. In theory, one could have a sen-
sory block with minimal motor blockade and still display sur-
gical anesthesia. Because our primary outcome was motor block
duration, we erred on the side of caution and retained only

FIGURE 5. Kaplan–Meier survival plot for the duration of analgesia. P = 0.048 (log-rank test). Dex, Dexamethasone.

332 © 2016 American Society of Regional Anesthesia and Pain Medicine

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Regional Anesthesia and Pain Medicine • Volume 41, Number 3, May-June 2016
subjects with minimal composite scores of 14 points. In a sim-
ilar effort to maximize precision, we discarded patients whose
blocks wore off during their sleep.
Our protocol contains some limitations. First, the durations
of sensorimotor block and postoperative analgesia axiomatically
depend on patient recall. Therefore, to minimize subjectivity, we
selected motor block as the primary outcome and circumvented
sleep. Second, our findings are specific to the adrenalized lido-
caine 1% bupivacaine 0.25% mix and ICB used in the current
study. Further trials are required to elucidate the role of IV and
PN dexamethasone for other LAs and other types of nerve blocks.
Third, although we measured analgesic duration, we did not
record breakthrough opioid consumption and opioid-related
adverse effects. Because our trial was carried out in 3 centers
and 2 countries, we feared that different patterns of opioid pre-
scription might have constituted a confounding variable. Fi-
nally, although no neural deficit was observed in the PN group
at 7 days, further studies are needed to validate the safety of
PN dexamethasone.
In conclusion, compared with its IV counterpart, PN dexa-
methasone (5 mg) provides longer motor block, sensory block,
and postoperative analgesia for US-guided ICB. Future dose-
finding studies are required to elucidate the optimal dose of
IV and PN dexamethasone.
ACKNOWLEDGMENTS
The authors thank Mr Derek Mitchell as well as Drs Richard
Bondy, Aida Gordon, Andrew Owen, Richard Robinson, and Gina
Wu for their invaluable assistance with patient recruitment.
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