The Facilitatory Effects of Intravenous

Dexmedetomidine on the Duration of Spinal

Anesthesia: A Systematic Review and Meta-Analysis
Faraj W. Abdallah, MD,* Amir Abrishami, MD,† and Richard Brull, MD, FRCPC‡

BACKGROUND: Central mechanisms have been proposed to explain the prolongation of effect
reported with the off-label use of dexmedetomidine as an adjuvant in local anesthetic admix-
tures. We evaluated whether IV dexmedetomidine can prolong the duration of sensory block
associated with spinal anesthesia.
METHODS: The authors searched MEDLINE, Embase, Cochrane Database of Systematic
Reviews, and Cochrane Central Register of Controlled Trials databases for randomized controlled
trials investigating the facilitatory effects of IV administration of dexmedetomidine (dexmedeto-
midine group) compared with placebo (control group) on single-injection local anesthetic-based
spinal anesthesia. Durations of sensory and motor block, sensory and motor block onset times,
postoperative pain scores, time to first analgesic request, analgesic consumption, and dexme-
detomidine-related side effects were evaluated. Results were combined using random effects
modeling when appropriate.
RESULTS: A total of 364 patients were analyzed from 7 intermediate to high-quality random-
ized controlled trials. When IV dexmedetomidine accompanied spinal anesthesia, sensory block
duration was prolonged by at least 34% (point estimate: 38%), P < 0.00001, motor block dura-
tion was prolonged by at least 17% (point estimate: 21%), P < 0.00001, and time to first anal-
gesic request was increased by at least 53% (point estimate: 60%), P < 0.00001. The use of
dexmedetomidine was associated with a 3.7-fold increase (95% confidence interval, 1.53–8.82,
P = 0.004) in transient reversible bradycardia. There was no difference in the incidence of hypo-
tension or postoperative sedation, and none of the patients experienced respiratory depression.
CONCLUSION: IV dexmedetomidine can prolong the duration of sensory block, motor block,
and time to first analgesic request associated with spinal anesthesia.   (Anesth Analg
2013;117:271–8)

D
exmedetomidine is a novel selective α-2 adrenocep-
tor agonist1 primarily used for IV sedation. The off-
label use of dexmedetomidine as a local anesthetic
adjuvant has been increasingly reported to prolong the
duration of anesthesia produced by single-injection neur-
axial2–6 and peripheral7–10 nerve blockade. Central mecha-
nisms11–13 have been proposed to explain this phenomenon,
suggesting that routes of administration other than intra-
thecal application may produce similar effects. In fact, cloni-
dine, another α-2 adrenoceptor agonist,14 has been shown
to prolong neuraxial15–19 and peripheral20–23 nerve blockade
when administered either as a local anesthetic admixture,
IV, or even orally. However, most trials examining the
effects of IV dexmedetomidine on the duration of regional
anesthesia are limited by their small sample size and have
From the *Department of Anesthesia, Women’s College Hospital, and
St. Michael’s Hospital, University of Toronto; †Department of Anesthesia,
University of Toronto; and ‡Department of Anesthesia, Women’s College
Hospital, and Toronto Western Hospital (University Health Network), Uni-
versity of Toronto, Toronto, Ontario, Canada.
Accepted for publication February 21, 2013.
Funding: Richard Brull, MD, FRCPC, is supported by the Merit Award Pro-
gram, Department of Anesthesia, University of Toronto.
The authors declare no conflicts of interest.
Reprints will not be available from the authors.
Address correspondence to Richard Brull, MD, FRCPC, Department of
Anesthesia, University of Toronto, Department of Anesthesia, Toronto West-
ern Hospital, 399 Bathurst St., Toronto, Ontario, Canada M5T 2S8. Address
e-mail to richard.brull@uhn.ca.
Copyright © 2013 International Anesthesia Research Society.
DOI: 10.1213/ANE.0b013e318290c566
generated quantitatively heterogeneous results.24–31 This
systematic review and meta-analysis primarily evaluated
whether IV dexmedetomidine can prolong the duration of
sensory block associated with spinal anesthesia.
METHODS
The Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA)32 recommendations were fol-
lowed in the preparation of this review.
Eligibility Criteria
We sought to identify randomized controlled trials (RCTs)
that investigated the facilitatory effects of IV administra-
tion of dexmedetomidine (dexmedetomidine group) com-
pared with placebo (control group) on single-injection
local anesthetic-based spinal anesthesia as a primary
or secondary outcome measure. RCTs were excluded if
dexmedetomidine was tested against an active compara-
tor26 that may also possess facilitatory effects on local
anesthetic action, if dexmedetomidine was administered
intrathecally as part of a local anesthetic admixture2 or
administered via a non-IV route,33–35 or no spinal blocks
were performed.24,36–39
Literature Search
RCTs were retrieved from the United States 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–July 2012).

July 2013 • Volume 117 • Number 1 www.anesthesia-analgesia.org 271

Effects of Intravenous Dexmedetomidine on Spinal Anesthesia

Table 1.  Trial Characteristics

Trial characteristics Quantity (n) Percentage
Source database
 Medline 4 57.1
  Hand search 1 14.3
  Google scholar 1 14.3
  Gray literature 1 14.3
Trial source journal
  Listed in index medicus 5 71.4
  Not listed in index medicus 2 28.6
Trial source country
 Jordan 2 28.6
 Korea 1 14.3
 Mexico 1 14.3
 Turkey 3 42.8
Jadad score
  5 (excellent quality) 4 57.1
 4 2 28.6
 3 1 14.3
 2 0 0
  1 (poor quality) 0 0
No. of subjects
 <50 0 0
 50–100 7 100
 >100 0 0
Age
  Adult (≥18 y) 7 100
  Pediatric (<18 y) 0 0
Gender
 Female 1 14.3
 Male 2 28.6
 Both 4 57.1
Figure 1. Preferred Reporting Items for Systematic Reviews and Disposition
Meta-Analyses (PRISMA) flow diagram depicting the flow of informa-  Inpatient 3 42.8
tion through the various phases of this systematic review. RCTs =  Outpatient 1 14.3
randomized controlled trials.  Both 1 14.3
 Unspecified 2 28.6
Timing of Dex administration
 Preblock 2 28.6
The search terms dexmedetomidine, medetomidine were  Postblock 5 71.4
used in combination with the search terms intravenous, Dex = dexmedetomidine; n = number of randomized controlled trials.
IV, systemic, and sedation. The results of the search
were combined by the Boolean operator AND with of sensory and motor block, pain visual analog scale scores,
medical subject headings spinal block/spinal anesthesia/ time to first analgesic request, postoperative analgesic con-
intrathecal anesthesia/subarachnoid block and the medical sumption, and dexmedetomidine-related adverse effects
subject headings analgesia/pain relief/pain control/ (hypotension, bradycardia, respiratory depression, and
pain prevention/and pain management. Additionally, postoperative sedation). Using a standardized data collec-
we hand-searched the bibliographies of relevant reviews tion form, data were extracted and recorded independently
and identified RCTs that met the inclusion criteria. The by the authors. Any discrepancies were resolved by rein-
search was restricted to articles in the English language. spection of the original data.
Unpublished trials were excluded. A final list of qualifying
studies was derived by consensus; the authors disagreed Meta-Analysis
over the eligibility of 1 trial,40 which was resolved by Data were entered into the statistical program (by FWA) and
majority vote. rechecked (by RB). When possible, meta-analytic techniques
(Revman 5.1, Cochrane Library, Oxford, England) were
used to combine the data. To facilitate clinical interpreta-
Data Collection and Presentation tion, the ratio of means, standard error, and 95% confidence
The quality of the reviewed RCTs was assessed indepen- intervals (CIs) were calculated for continuous outcomes
dently by 2 of the authors (FWA and RB) using the Jadad that examined change from baseline by measuring the time-
score,41 with a final score assigned for each trial by consen- to-event.46,47 Random effect modeling48 was used to analyze
sus. The outcomes sought in each trial assessed included the remaining continuous and dichotomous outcomes. The
block characteristics, postoperative analgesia,42,43 and the odds ratio and 95% CI were calculated for the dichoto-
common dexmedetomidine-related adverse effects.44,45 For mous outcomes, whereas the standardized mean difference
the purposes of the present review, we sought to evaluate and 95% CI were calculated for the continuous outcomes.
the durations of sensory and motor block, the onset times Differences were considered statistically significant when

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the 95% CI did not include 0 for the standardized mean
difference and 1 for odds ratio. The I2 statistic was used to
assess heterogeneity.49
RESULTS
We identified 7 intermediate to high-quality trials29,31,40,50–53
that investigated the facilitatory effects of IV
dexmedetomidine on spinal anesthesia and met our
inclusion criteria. The 7 trials included 364 patients, 184 in
the dexmedetomidine group and 180 in the control group,
who qualified for analysis. Figure 1 summarizes the search
results, including the RCTs retrieved, excluded, and presently
reviewed. Tables 1 and 2 summarize the characteristics and
the outcomes sought in each of the reviewed trials.
Sensory Block Duration
The duration of sensory block was assessed in all 7 trials
and is presented in Figure 2. When IV dexmedetomidine
was administered to patients undergoing surgery under
spinal anesthesia, a prolongation of the sensory block dura-
tion was observed compared with placebo. This prolonga-
tion, expressed as the lower CI limit (point estimate), was at
least 34% (point estimate: 38%), P < 0.00001, I2 = 87%.
Block Characteristics
The duration of motor block was assessed in all 7 trials
and is presented in Figure 3. Motor block was prolonged
by at least 17% (point estimate: 21%), P < 0.00001, I2 = 85%
in patients receiving IV dexmedetomidine compared with
placebo (Table 3).
Qualitatively, only 2 trials40,51 examined sensory block
onset time and detected no difference between the dexme-
detomidine and control groups. The onset time of motor
block was assessed by 2 trials;50,51 whereas one50 described
no difference in the onset time of motor block without pro-
viding the raw data, another51 reported a 1-minute differ-
ence in favor of the dexmedetomidine group.
Postoperative Analgesia
Postoperative pain scores and time to first analgesic
request were evaluated by 229,31 and 329,31,50 trials,
respectively. IV dexmedetomidine reduced postoperative
visual analog scale pain scores at 6 hours by 6 mm (95%
CI, −1.19 to −0.03, P = 0.04), or a relative reduction of
61%. IV dexmedetomidine also prolonged the time to first
analgesic request by at least 53% (point estimate: 60%),
P < 0.00001, I2 = 98% in patients undergoing surgery under
spinal anesthesia (Table 3).
None of the trials examined analgesic consumption,
although 1 trial29 reported fewer patients requesting post-
operative analgesic supplementation in the dexmedetomi-
dine group.
Dexmedetomidine-Related Adverse Effects
Because of the diversity of definitions of dexmedetomi-
dine-related adverse effects used by investigators, we
reported the results of these outcomes as “standardized
units.” Hypotension and bradycardia were reported in
all 7 trials,29,31,40,50–53 respiratory depression was examined
July 2013 • Volume 117 • Number 1 www.anesthesia-analgesia.org   273
in 6,29,31,40,51–53 and postoperative sedation was assessed in
4.29,51–53 Although there was no difference in the incidence
of hypotension and postoperative sedation between the
groups, bradycardia was more common (3.7-fold increase,
95% CI, 1.53–8.82, P = 0.004) among patients who received
IV dexmedetomidine (Table 3).
The incidence of bradycardia was higher in trials where
the dexmedetomidine initial loading dose was infused over
a shorter duration, such as 531 or 1051 minutes, compared
with those trials where the initial loading dose was admin-
istered over 20 minutes.50 Bradycardia was transient and
easily reversed with IV atropine; no delayed bradycardia
was reported. None of the patients in the reviewed trials
experienced serious respiratory complications.
Other Outcomes
The maximal level of sensory block produced by spinal
anesthesia was reported in 5 trials.29,31,40,50,51 Quantitative
analysis of the pooled results showed no difference in maxi-
mal sensory block level between the dexmedetomidine and
control groups (Table 3).
DISCUSSION
Our review suggests that IV dexmedetomidine can pro-
long the duration of sensory block when administered to
patients undergoing spinal anesthesia. Additionally, IV dex-
medetomidine can prolong the duration of motor block to
a lesser extent and delay the time to first analgesic request
after spinal anesthesia. These effects are accompanied by an
increased risk of transient reversible bradycardia.
Clonidine, another α-2 adrenoceptor agonist, has long
been known to prolong spinal anesthesia when admin-
istered IV.18,54,55 Compared with clonidine,18 our findings
suggest that IV dexmedetomidine produces a greater
degree of differential blockade by preferentially block-
ing myelinated A α-fibers involved in sensory conduction
over unmyelinated C fibers involved in motor conduction.
Such selectivity may be useful in settings where prolonged
analgesia but not necessarily prolonged motor block is
desirable, such as with low-dose spinal anesthesia used in
cesarean deliveries.56 IV dexmedetomidine may actually
serve a dual purpose in the setting of spinal anesthesia,
both by enhancing the local anesthetic effects and provid-
ing intraoperative sedation, the latter often implicated in
unsuccessful neuraxial techniques.57 Although the present
analysis failed to detect any differences in postoperative
sedation between groups, this finding most likely reflects
the very short half-life of IV dexmedetomidine,58 which is
one of several unique features that makes this drug such a
useful sedative drug.
The results of this review are subject to several
limitations. First, the limited number of small trials
included in this review is marked by considerable
heterogeneity that may undermine the generalizability
of our results. The range of doses and types of local
anesthetics used for spinal anesthesia as well as the
doses of IV dexmedetomidine may also affect the reliable
translation of our results into clinical practice. Specifically,
initial loading doses of dexmedetomidine varied between
Effects of Intravenous Dexmedetomidine on Spinal Anesthesia

Table 2.  Trial Outcomes

IV dexmedetomidine
Jadad Local
Author/year score Surgery N Groups (n) anesthetic Bolus Maintenance
Tekin et al., 4 Lower limb, 60 1. IV Dex + spinal prilocaine (30) 80 mg 1. 1 µg/kg over 10 1. 0.4 µg/kg/h
200740 abdominal, prilocaine min over 50 min
anorectal in 4 mL
2. IV NS + spinal prilocaine (30) 2. Matched volume 2. Matched volume
Whizar-Lugo 3 Abdominal 70 1. IV Dex + spinal bupivacaine (25) 15 mg 1. 1 µg/kg over 20 1. 0.5 µg/kg/h
et al., hysterectomy bupivacaine min through surgery
200750 in 3 mL
2. IV clonidine + spinal bupivacaine 2. 4 µg/kg over 20 2. Matched volume
(25) min
3. IV NS + spinal bupivacaine (20) 3. None 3. Matched volume
Al-Mustafa 5 Urologic 48 1. IV Dex + spinal bupivacaine (24) 12.5 mg 1. 1 µg/kg over 10 1. 0.5 µg/kg/h
et al., bupivacaine min through surgery
200953 in 2.5 mL
2. IV NS + spinal bupivacaine (24) 2. Matched volume 2. Matched volume
Kaya et al., 5 TURP 75 1. IV Dex + spinal bupivacaine (25) 15 mg 1. 0.5 µg/kg over 10 None
201029 bupivacaine min
in 3 mL
2. IV midazolam + spinal 2. 0.05 mg/kg over
bupivacaine (25) 10 min
3. IV NS + spinal bupivacaine (25) 3. Matched volume
Elcicek 5 Lower extremity 60 1. IV Dex + spinal ropivacaine (30) 22.5 mg 1. 1 µg/kg over 10 1. 0.4 µg/kg/h
et al., ropivacaine min over 50 min
201051 in 4 mL
2. IV NS + spinal ropivacaine (30) 2. Matched volume Matched volume
Al-Oweidi 4 Knee replacement 75 1. IV Dex + spinal bupivacaine (25) 12.5 mg 1. 1 µg/kg over 10 1. 0.2–0.5 µg/kg/h
et al., bupivacaine min
201152 2. IV propofol + spinal bupivacaine in 2.5 mL 2. 4 mg/kg/h over 2. 0.5–2 mg/kg/h
(25) 10 min
3. IV NS + spinal bupivacaine (25) 3. None
Hong et al., 5 TURP 51 1. IV Dex + spinal bupivacaine (25) 6 mg 1. 1 µg/kg over 5 min 1. None
201231 2. IV NS + spinal bupivacaine (26) bupivacaine 2. Matched volume
2. None
in 1.2 mL
Dex = dexmedetomidine; N/D = not defined; NS = not significant; Postop = postoperative; TURP = transurethral resection of prostate tumor.

0.529 and 1 µg/kg;31,40,50–53 most trials also included a length of surgery50,53 (Table 2). Furthermore, the duration
maintenance dexmedetomidine infusion,40,50–53 with rates of administration of the initial dexmedetomidine dose
varying between and 0.252 and 0.550 µg/kg/h, over a varied between 5,31 10,29,40,51–53 and 2050 minutes among the
duration varying between 50 minutes40,51 and the entire various trials. Although these variations likely reflect the

Figure 2. Forest plot depicting sensory block duration. The individual trials’ ratio of means, standard error, and the pooled estimates of the
ratio of means are shown. The 95% confidence interval (CI) are shown as lines for individual studies and as diamonds for pooled estimates.

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www.anesthesia-analgesia.org anesthesia & analgesia
 Table 2.  Continued
Block characteristics Analgesic outcomes Dex-related adverse effects
Time
Sensory Sensory Motor Motor to first
Primary block block block block Postop analgesic Analgesic Postop Respiratory
outcome onset duration onset duration Pain request consumption Hypotension Bradycardia sedation depression
N/D • • • • • •

N/D • • • • • • •

N/D • • • • • •

Sensory block • • • • • • • • •
duration

N/D • • • • • • • •

N/D • • • • •

Sensory block • • • • • • • •
duration

absence of dose-ranging studies investigating the optimal isolated boluses in the absence of maintenance infusion.
dose of IV dexmedetomidine, it is nonetheless noteworthy The lack of standardized assessment of sensory block
that a significant prolongation of anesthetic effect was duration (e.g., time to 2-dermatome regression,29,31,40,51 time
observed with doses as low as 0.5 µg/kg29 administered as to S1 regression,52,53 and to L5–S2 regression)50 may also

Figure 3. Forest plot depicting motor block duration. The individual trials’ ratio of means, standard error, and the pooled estimates of the
ratio of means are shown. The 95% confidence interval (CI) are shown as lines for individual studies and as diamonds for pooled estimates.

July 2013 • Volume 117 • Number 1 www.anesthesia-analgesia.org   275

Effects of Intravenous Dexmedetomidine on Spinal Anesthesia

Table 3.  Results
Outcome Studies included Dex mean Control mean Ratio of means P-value for P-value for I2 test for
(95% confidence statistical heterogeneity heterogeneity
interval) significance
Sensory block 29,31,40,50–53 183.76 130.37 1.38 (1.34–1.42) <0.00001 <0.00001 87%
duration (min)
Sensory block 40,51  11.75  11.58 1.00 (0.93–1.08) <0.00001 0.83  0%
onset (min)
Motor block 29,31,40,50–53 200.63 165.31 1.21 (1.17–1.25) <0.00001 <0.00001 85%
duration
(min)
Time to first 29,31,50 277.33 131.35 1.60 (1.53–1.67) <0.00001 <0.00001 98%
analgesic
request (min)
Outcome Studies included Dex Control Odds ratio or P-value for P-value for I2 test for
mean or n/N mean or n/N weighed statistical heterogeneity heterogeneity
mean (95% significance
confidence
interval)

Maximum 29,31,40,50,51 T 7.90 T 8.40 −0.39 (−1.32 to 0.55) 0.42 <0.00001 91%
block height
(dermatomes)
Postoperative 29,31 1.85 2.62 −0.61 (−1.19 to 0.03) 0.04 0.63 N/A
pain scores
at 6 h (mm)
Incidence of 29,31,40,50–53 12/184 13/181 1.03 (0.38–2.79) 0.95 0.32 14%
hypotension
(n/N)
Incidence of 29,31,40,50–53 34/180 9/183 3.67 (1.53–8.82) 0.004 0.36 9%
bradycardia
(n/N)
Incidence of 29,51–53 5/79 0/79 6.61 (0.76–57.22) 0.09 0.86 0%
postoperative
sedation (n/N)
The ratio of means calculations were performed using the methods described by Friedrich and colleagues.46,47
Dex = dexmedetomidine; N/A = not applicable.

limit the generalizability of our results. Similar variability
was observed in the measurement of other outcomes such
as motor block duration and time to first analgesic.
In summary, IV dexmedetomidine can prolong the dura-
tion of sensory and motor blocks as well as the time to first
analgesic request of spinal anesthesia. Our findings sug-
gest that the administration of IV dexmedetomidine may
limit the role, if any, for the direct intrathecal application of
dexmedetomidine, which lacks adequate safety data at the
present time. E
DISCLOSURES
Name: Faraj W. Abdallah, MD.
Contribution: This author helped design and conduct the
study, analyze the data, and write the manuscript.
Attestation: Faraj W. Abdallah has seen the original study
data, reviewed the analysis of the data, approved the final
­manuscript, and is the author responsible for archiving the
study files.
Name: Amir Abrishami, MD.
Contribution: This author helped analyze the data.
Attestation: Amir Abrishami has seen the original study
data, reviewed the analysis of the data, approved the final
­manuscript, and is the author responsible for archiving the
study files.
Name: Richard Brull, MD, FRCPC.
Contribution: This author helped design and conduct the
study, analyze the data, and write the manuscript.
Attestation: Richard Brull has seen the original study
data, reviewed the analysis of the data, approved the final
­manuscript, and is the author responsible for archiving the
study files.
This manuscript was handled by: Terese T. Horlocker, MD.
ACKNOWLEDGMENTS
The authors thank Dr. Jan O. Friedrich, from the Departments of
Medicine, Critical Care, and the Keenan Research Centre in the
Li Ka Shing Knowledge Institute at the St. Michael’s Hospital,
University of Toronto, Canada, for his valuable contribution.
REFERENCES
1. Segal IS, Vickery RG, Walton JK, Doze VA, Maze M.
Dexmedetomidine diminishes halothane anesthetic require-
ments in rats through a postsynaptic alpha 2 adrenergic recep-
tor. Anesthesiology 1988;69:818–23
2. Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD,
Alameddine MM, Al-Yaman R, Bulbul M, Baraka AS. Effect
of low-dose dexmedetomidine or clonidine on the character-
istics of bupivacaine spinal block. Acta Anaesthesiol Scand
2006;50:222–7
3. Al-Mustafa MM, Abu-Halaweh SA, Aloweidi AS, Murshidi
MM, Ammari BA, Awwad ZM, Al-Edwan GM, Ramsay MA.
Effect of dexmedetomidine added to spinal bupivacaine for
urological procedures. Saudi Med J 2009;30:365–70

276   
www.anesthesia-analgesia.org anesthesia & analgesia
 4. Eid H, Shafie M, Youssef H. Dose-related prolongation of
hyperbaric bupivacaine spinal anesthesia by dexmedetomi-
dine. Ain Shams J Anesthesiology 2011;4:83–95
5. Gupta R, Bogra J, Verma R, Kohli M, Kushwaha JK, Kumar S.
Dexmedetomidine as an intrathecal adjuvant for postoperative
analgesia. Indian J Anaesth 2011;55:347–51
6. Shukla D, Verma A, Agarwal A, Pandey HD, Tyagi C.
Comparative study of intrathecal dexmedetomidine with intra-
thecal magnesium sulfate used as adjuvants to bupivacaine.
J Anaesthesiol Clin Pharmacol 2011;27:495–9
7. Esmaoglu A, Yegenoglu F, Akin A, Turk CY. Dexmedetomidine
added to levobupivacaine prolongs axillary brachial plexus
block. Anesth Analg 2010;111:1548–51
8. Gandhi R, Shah A, Patel I. Use of dexmedetomidine along with
bupivacaine for brachial plexus block. National J Med Res
2012;2:67–9
9. Kaygusuz K. Effects of adding dexmedetomidine to levobupi-
vacaine in axillary brachial plexus block. Curr Ther Res Clin
Exp 2012;73:103–11
10. Ammar AS, Mahmoud KM. Ultrasound-guided single injection
infraclavicular brachial plexus block using bupivacaine alone
or combined with dexmedetomidine for pain control in upper
limb surgery: A prospective randomized controlled trial. Saudi
J Anaesth 2012;6:109–14
11. Jorm CM, Stamford JA. Actions of the hypnotic anaesthetic,
dexmedetomidine, on noradrenaline release and cell firing in
rat locus coeruleus slices. Br J Anaesth 1993;71:447–9
12. Guo TZ, Jiang JY, Buttermann AE, Maze M. Dexmedetomidine
injection into the locus ceruleus produces antinociception.
Anesthesiology 1996;84:873–81
13. Weinbroum AA, Ben-Abraham R. Dextromethorphan and
dexmedetomidine: new agents for the control of perioperative
pain. Eur J Surg 2001;167:563–9
14. Eisenach JC, De Kock M, Klimscha W. alpha(2)-adrenergic
agonists for regional anesthesia. A clinical review of clonidine
(1984-1995). Anesthesiology 1996;85:655–74
15. Niemi L. Effects of intrathecal clonidine on duration of bupi-
vacaine spinal anaesthesia, haemodynamics, and postopera-
tive analgesia in patients undergoing knee arthroscopy. Acta
Anaesthesiol Scand 1994;38:724–8
16. Liu S, Chiu AA, Neal JM, Carpenter RL, Bainton BG, Gerancher
JC. Oral clonidine prolongs lidocaine spinal anesthesia in
human volunteers. Anesthesiology 1995;82:1353–9
17. De Kock M, Gautier P, Fanard L, Hody JL, Lavand’homme
P. Intrathecal ropivacaine and clonidine for ambulatory
knee arthroscopy: a dose-response study. Anesthesiology
2001;94:574–8
18. Rhee K, Kang K, Kim J, Jeon Y. Intravenous clonidine pro-
longs bupivacaine spinal anesthesia. Acta Anaesthesiol Scand
2003;47:1001–5
19. Strebel S, Gurzeler JA, Schneider MC, Aeschbach A, Kindler
CH. Small-dose intrathecal clonidine and isobaric bupivacaine
for orthopedic surgery: a dose-response study. Anesth Analg
2004;99:1231–8, table of contents
20. Mannion S, Hayes I, Loughnane F, Murphy DB, Shorten GD.
Intravenous but not perineural clonidine prolongs postop-
erative analgesia after psoas compartment block with 0.5%
levobupivacaine for hip fracture surgery. Anesth Analg
2005;100:873–8, table of contents
21. Casati A, Magistris L, Fanelli G, Beccaria P, Cappelleri G,
Aldegheri G, Torri G. Small-dose clonidine prolongs postop-
erative analgesia after sciatic-femoral nerve block with 0.75%
ropivacaine for foot surgery. Anesth Analg 2000;91:388–92
22. Singelyn FJ, Dangoisse M, Bartholomée S, Gouverneur JM.
Adding clonidine to mepivacaine prolongs the duration of
anesthesia and analgesia after axillary brachial plexus block.
Reg Anesth 1992;17:148–50
23. YaDeau JT, LaSala VR, Paroli L, Kahn RL, Jules-Elysée KM,
Levine DS, Wukovits BL, Lipnitsky JY. Clonidine and anal-
gesic duration after popliteal fossa nerve blockade: random-
ized, double-blind, placebo-controlled study. Anesth Analg
2008;106:1916–20
24. Wahlander S, Frumento RJ, Wagener G, Saldana-Ferretti B,
Joshi RR, Playford HR, Sladen RN. A prospective, double-blind,
July 2013 • Volume 117 • Number 1 www.anesthesia-analgesia.org   277
randomized, placebo-controlled study of dexmedetomidine
as an adjunct to epidural analgesia after thoracic surgery.
J Cardiothorac Vasc Anesth 2005;19:630–5
25. Esmaoglu A, Mizrak A, Akin A, Turk Y, Boyaci A. Addition of
dexmedetomidine to lidocaine for intravenous regional anaes-
thesia. Eur J Anaesthesiol 2005;22:447–51
26. Magalhães E, Ladeira LC, Govêia CS, Espíndola BV. Intravenous
dexmedetomidine for sedation does not interfere with sensory
and motor block duration during spinal anesthesia. Rev Bras
Anestesiol 2006;56:1–7
27. Akin S, Aribogan A, Arslan G. Dexmedetomidine as an adjunct
to epidural analgesia after abdominal surgery in elderly inten-
sive care patients: A prospective, double-blind, clinical trial.
Curr Ther Res Clin Exp 2008;69:16–28
28. Rutkowska K, Knapik P, Misiolek H. The effect of dexmedeto-
midine sedation on brachial plexus block in patients with end-
stage renal disease. Eur J Anaesthesiol 2009;26:851–5
29. Kaya FN, Yavascaoglu B, Turker G, Yildirim A, Gurbet A,
Mogol EB, Ozcan B. Intravenous dexmedetomidine, but not
midazolam, prolongs bupivacaine spinal anesthesia. Can J
Anaesth 2010;57:39–45
30. Mizrak A, Gul R, Erkutlu I, Alptekin M, Oner U. Premedication
with dexmedetomidine alone or together with 0.5% lidocaine
for IVRA. J Surg Res 2010;164:242–7
31. Hong JY, Kim WO, Yoon Y, Choi Y, Kim SH, Kil HK. Effects
of intravenous dexmedetomidine on low-dose bupivacaine
spinal anaesthesia in elderly patients. Acta Anaesthesiol Scand
2012;56:382–7
32. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group.
Preferred reporting items for systematic reviews and meta-
analyses: the PRISMA statement. PLoS Med 2009;6:e1000097
33. Cheung CW, Ng KF, Liu J, Yuen MY, Ho MH, Irwin MG.
Analgesic and sedative effects of intranasal dexmedetomidine
in third molar surgery under local anaesthesia. Br J Anaesth
2011;107:430–7
34. Al-Metwalli RR, Mowafi HA, Ismail SA, Siddiqui AK,
Al-Ghamdi AM, Shafi MA, El-Saleh AR. Effect of intra-articular
dexmedetomidine on postoperative analgesia after arthroscopic
knee surgery. Br J Anaesth 2008;101:395–9
35. El-Hamamsy M, Dorgham D. Intra-articular adjuvant anal-
gesics following knee arthroscopy: comparison between
dexmedetomidine and fentanyl. Res J Med Med Sci 2009;4:
355–60
36. Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of
dexmedetomidine versus morphine for postoperative analge-
sia after major inpatient surgery. Anesth Analg 2004;98:153–8
37. Sarhan TM. Effect of intravenous administration of dexmedeto-
midine on the duration of caudal analgesia with ropivacaine in
pediatrics. Alex J Anaesth Intensive Care 2005;8:28–32
38. Lin TF, Yeh YC, Lin FS, Wang YP, Lin CJ, Sun WZ, Fan SZ.
Effect of combining dexmedetomidine and morphine for intra-
venous patient-controlled analgesia. Br J Anaesth 2009;102:
117–22
39. Akin A, Ocalan S, Esmaoglu A, Boyaci A. The effects of cau-
dal or intravenous clonidine on postoperative analgesia pro-
duced by caudal levobupivacaine in children. Paediatr Anaesth
2010;20:350–5
40. Tekin M, Kati I, Tomak Y, Kisli E. Effect of dexmedetomidine IV
on the duration of spinal anesthesia with prilocaine: A double-
blind, prospective study in adult surgical patients. Curr Ther
Res Clin Exp 2007;68:313–24
41. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ,
Gavaghan DJ, McQuay HJ. Assessing the quality of reports of
randomized clinical trials: is blinding necessary? Control Clin
Trials 1996;17:1–12
42. Liu SS, Warren DT, Wu CL, Ballantyne JC, Ginsberg B, Rathmell
JP, Rosenquist RW, Viscusi ER. A lovely idea: forming an ASRA
Acute Postoperative Pain (AcutePOP) database. Reg Anesth
Pain Med 2006;31:291–3
43. Liu SS, Wu CL, Ballantyne JC, Buvanendran A, Rathmell JP,
Warren DT, Viscusi ER, Ginsberg B, Rosenquist RW, Yadeau
JT, Liguori GA. Where in the world is ASRA AcutePOP? Reg
Anesth Pain Med 2009;34:269–74
Effects of Intravenous Dexmedetomidine on Spinal Anesthesia
44. Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The
effects of increasing plasma concentrations of dexmedetomi-
dine in humans. Anesthesiology 2000;93:382–94
45. Aantaa RE, Kanto JH, Scheinin M, Kallio AM, Scheinin H.
53. Al-Mustafa MM, Badran IZ, Abu-Ali HM, Al-Barazangi BA,
Dexmedetomidine premedication for minor gynecologic sur-
gery. Anesth Analg 1990;70:407–13
46. Friedrich JO, Adhikari NK, Beyene J. The ratio of means method
as an alternative to mean differences for analyzing continuous
outcome variables in meta-analysis: a simulation study. BMC
Med Res Methodol 2008;8:32
47. Friedrich JO, Adhikari NK, Beyene J. Ratio of means for analyz-
ing continuous outcomes in meta-analysis performed as well as
mean difference methods. J Clin Epidemiol 2011;64:556–64
48. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control
Clin Trials 1986;7:177–88
49. Higgins JP, Thompson SG. Quantifying heterogeneity in a
meta-analysis. Stat Med 2002;21:1539–58
50. Whizar-Lugo V, Gómez-Ramírez IA, Cisneros-Corral R,
Martínez-Gallegos N. Intravenous dexmedetomidine vs. intra-
venous clonidine to prolong bupivacaine spinal anesthesia. A
double blind study. Anestesia En México 2007;19:143–6
51. Elcicek K, Tekin M, Kati I. The effects of intravenous dex-
medetomidine on spinal hyperbaric ropivacaine anesthesia.
J Anesth 2010;24:544–8
52. Al-Oweidi AS, Al-Mustafa MM, Al Ajlouni JM, Mas’ad DF,
Hamdan MQ, Alghanem SA, Qudaisat IY, Abu Halaweh SA,
278   
www.anesthesia-analgesia.org
Massad IM. Intravenous dexmedetomidine or propofol adju-
vant to spinal anesthesia in total knee replacement surgery.
Jordan Med J 2011;45:174–82
Massad IM, Al-Ghanem SM. Intravenous dexmedetomi-
dine prolongs bupivacaine spinal analgesia. Middle East J
Anesthesiol 2009;20:225–31
54. Bernard JM, Kick O, Bonnet F. Comparison of intravenous and
epidural clonidine for postoperative patient-controlled analge-
sia. Anesth Analg 1995;81:706–12
55. Hansen TG, Henneberg SW, Walther-Larsen S, Lund J,
Hansen M. Caudal bupivacaine supplemented with cau-
dal or intravenous clonidine in children undergoing hypo-
spadias repair: a double-blind study. Br J Anaesth 2004;92:
223–7
56. Arzola C, Wieczorek PM. Efficacy of low-dose bupivacaine in
spinal anaesthesia for Caesarean delivery: systematic review
and meta-analysis. Br J Anaesth 2011;107:308–18
57. Brown DL. Spinal, epidural, and caudal anesthesia. In: Miller
RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young
WL, eds. Miller’s Anesthesia. 7th ed. Philadelphia: Elsevier
Churchill Livingstone, 2009;1611–38
58. Dyck JB, Maze M, Haack C, Vuorilehto L, Shafer SL. The
pharmacokinetics and hemodynamic effects of intravenous
and intramuscular dexmedetomidine hydrochloride in adult
human volunteers. Anesthesiology 1993;78:813–20
anesthesia & analgesia