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Available online at www.sciencedirect.com

journal homepage: www.JournalofSurgicalResearch.com

Dexmedetomidine attenuates tourniquet-induced

hyperdynamic response in patients undergoing lower limb
surgeries: A randomized controlled study

Hsuan-Chih Lao, MD, MS,a,b Pei-Shan Tsai, PhD,c Jung-Yuan Su, MD,d
Tiew-Guan Kwok, MD,d and Chun-Jen Huang, MD, PhDe,f,*
a
Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan
b
School of Medicine, National Yang-Ming University, Taipei, Taiwan
c
Graduate Institute of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
d
Department of Orthopedics, Mackay Memorial Hospital, Taipei, Taiwan
e
Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei Branch, 289, Jianguo Road, Sindian District,
New Taipei City 231, Taipei, Taiwan
f
School of Medicine, Tzu Chi University, Hualien, Taiwan

article info abstract

Article history: Background: Activation of sympathetic nervous system has a crucial role in mediating the
Received 21 August 2011 pneumatic tourniquet inflation induced hyperdynamic response. Dexmedetomidine,
Received in revised form a selective a2-adrenergic receptor agonist, has potent sympatholytic effects. We conducted
28 December 2011 this prospective, randomized, placebo-controlled, double-blinded study to elucidate the
Accepted 4 January 2012 effects of dexmedetomidine on attenuating the tourniquet-induced hyperdynamic
Available online 4 April 2012 response during general anesthesia.
Materials and methods: We included a total of 72 healthy adult patients undergoing
Keywords: elective lower limb surgery. Under general anesthesia, patients were randomized to the
Dexmedetomidine dexmedetomidine or the control group (n ¼ 36 in each group). The dexmedetomidine
Tourniquet group received a loading dose of dexmedetomidine (0.8 mg$kg1 over 10 min) followed by
Hypertension continuous infusion of dexmedetomidine (0.4 mg$kg1.h1) until tourniquet deflation.
Lower limb The control group received normal saline instead. We compared tourniquet-induced
Orthopedic surgery changes in hemodynamic parameters between groups to elucidate the effects of
dexmedetomidine.
Results: Tourniquet inflation induced significant increases in hemodynamic parameters,
including heart rate, systolic arterial pressure, mean arterial pressure, diastolic arterial
pressure, rate pressure product, cardiac output, and stroke volume in the control group.
The effects of tourniquet inflation on increasing hemodynamic parameters were signifi-
cantly attenuated by dexmedetomidine: heart rate (P < 0.001), systolic arterial pressure
(P ¼ 0.002), mean arterial pressure (P ¼ 0.042), diastolic arterial pressure (P ¼ 0.012), rate
pressure product (P < 0.001), and cardiac output (P ¼ 0.001) of the dexmedetomidine group

Part of the study results were presented at the Annual Meeting of the American Society of Anesthesiologists, Orlando, Florida,
October 18e22, 2008.
* Corresponding author. Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei Branch, 289, Jianguo Rd., Sindian
District, New Taipei City 231, Taiwan. Tel.: þ1 886 2 66289779, ext. 2639; fax: þ1 886 2 66289009.
E-mail address: huangcj1112@gmail.com (C.-J. Huang).
0022-4804/$ e see front matter ª 2013 Elsevier Inc. All rights reserved.
doi:10.1016/j.jss.2012.01.008
e100 j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 9 ( 2 0 1 3 ) e 9 9 ee 1 0 6
were significantly lower than those of the control group. However, the stroke volume of
these groups was comparable.
Conclusions: Dexmedetomidine attenuates tourniquet-induced hyperdynamic response in
general anesthesia patients undergoing lower limb surgeries.
1. Introduction
Pneumatic tourniquet is widely used in lower limb surgery to
provide optimal operating conditions [1]. However, tourniquet
inflation can induce a hyperdynamic response that may be
resistant to therapies such as analgesic drugs, antihyperten-
sive drugs, and increases in anesthesia depth [2,3]. Although
mechanisms underlying the tourniquet-induced hyperdy-
namic response are not completely understood, augmented
sympathetic outflow caused by tourniquet inflation has been
proposed as an essential mechanism [4,5]. The a2-adrenergic
receptors are present in the central and peripheral nervous
system at autonomic ganglion as well as presynaptic and
postsynaptic sites [6]. Activation of the a2-adrenergic recep-
tors significantly decreases activity of the sympathetic
nervous system [7].
Dexmedetomidine is a selective, short-acting, agonist of
the a2-adrenergic receptors [8]. In addition to sympatholytic
effects, dexmedetomidine has antihypertensive, anxiolytic,
sedative, and analgesic effects [7]. Dexmedetomidine has
been used clinically as an adjunct to anesthesia, analgesia,
and intensive care unit sedation [7]. Theoretically, dexmede-
tomidine might exert significant effects on attenuating
tourniquet-induced hyperdynamic response. To elucidate
further, we conducted this randomized, placebo-controlled,
double-blinded study with the hypothesis that dexmedeto-
midine can attenuate the tourniquet-induced hyperdynamic
response in patients undergoing lower limb surgery.
2. Materials and methods
2.1. Participants
The Human Research Review Committee, Mackay Memorial
Hospital (MMH-I-S-338) approved this prospective, random-
ized, placebo-controlled, double-blinded study, which was
conducted in Mackay Memorial Hospital, a tertiary referral
teaching hospital in Taipei, Taiwan, between August 2007 and
December 2008. We approached all eligible patients for
recruitment before te operation and enrolled them after
obtaining written informed consent. Inclusion criteria were:
adult patients (18e75 y old), with American Society of Anes-
thesiologists physical status I or II, who were scheduled for
elective orthopedic lower limb surgeries and required pneu-
matic tourniquet application during surgeries. We excluded
patients if they were taking adrenergic or cholinergic agents.
We also excluded patients with fever (38 C), leucocytosis
(white blood cells  10,000 cells$ml1), anemia (hematocrit
< 20%), or obesity (body mass index > 30 kg.m2). In addition,
we excluded patients with a history of hypertension, cardiac
arrhythmia, congestive heart failure, diabetes mellitus, renal
ª 2013 Elsevier Inc. All rights reserved.
dysfunction, hepatic dysfunction, or allergy to dexmedeto-
midine (or other a2-agonist agents). We also excluded patients
with expected tourniquet time of <60 min or >150 min.
Because no previous study was available regarding the
effect of dexmedetomidine effect in this regard, we estimated
the sample size based on previous data derived from a study
on another widely used a2-adrenergic receptor agonist,
clonidine [5]. Previous data revealed that mean arterial pres-
sure (MAP) after tourniquet deflation in patients who received
clonidine was significantly lower than those who received
normal saline (84  11 versus 71  8 mm Hg) [5]. Based on these
data (expected differences in means, 13; expected standard
deviation, 9.5), power analysis revealed that a sample size of
10 patients per group was sufficient to detect a statistically
significant between group difference, with an alpha of 0.05
and a power of 82.5%. Nevertheless, because the estimation
was based on clonidine data, we decided to include at least 10
patients per group. By the end of the study period approved by
the Human Research Review Committee of our institute,
a total of 36 patients per group were included. We conducted
patient enrollment and subsequent allocation as illustrated in
the CONSORT diagram (Fig. 1).
2.2. Hemodynamic monitoring
We employed continuous electrocardiography (ECG) and
noninvasive blood pressure with arm cuff (NIBP) to measure
heart rate (HR), systolic arterial pressure (SAP), MAP, and
diastolic arterial pressure (DAP). In addition, we noninvasively
monitored cardiac output (CO) and stroke volume (SV) us-
ing the Finometer, a noninvasive hemodynamic monitoring
device (TNO Biomedical Instrumentation, Amsterdam, The
Netherlands). We performed validation of the Finometer using
upper-arm cuff return-to-flow measurement to calibrate
blood pressure, according to the manufacturer’s manual.
Myocardial oxygen consumption can be estimated by calcu-
lating the rate pressure product (RPP) (i.e., HR  SAP) [9]. We
thus also calculated RPP in this study.
2.3. Anesthetic management
We applied standard monitoring devices, including electro-
cardiogram, noninvasive blood pressure monitoring, pulse
oximetry, and capnography. After receiving premedication
with midazolam (0.035 mg$kg1, intravenously [IV]) and
hydration with Ringer’s lactate solution (500 mL), baseline
hemodynamics were measured. We induced general anes-
thesia with fentanyl (2 mg$kg1, IV) and propofol (2 mg$kg1, IV).
We used a bispectral index monitor (BIS) (Aspect A1000
monitor; Medical Systems, Natick, MA) to monitor anesthesia
depth. We used rocuronium (1 mg$kg1, IV) to facilitate
tracheal intubation. Tracheal intubation was performed after
 j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 9 ( 2 0 1 3 ) e 9 9 ee 1 0 6
Fig. 1 e The CONSORT diagram showing patients’ flow through the study.
loss of response to train-of-four with neuromuscular stimu-
lation and a BIS index <50 was achieved. After tracheal intu-
bation, we controlled ventilation with a tidal volume of
10 mL$kg1 and adjusted the respiratory rate to maintain an
end-tidal carbon dioxide of 35e40 mm Hg. All patients’ lungs
were mechanically ventilated with 4 L$min1 fresh gas (50%
air:50% O2). We maintained anesthesia with sevoflurane and
adjusted the concentration was to achieve a BIS index of 40e45.
2.4. Experimental protocols
An anesthesiologist who was involved only in preparing the
medication in a 100-mL syringe randomly allocated patients to
the dexmedetomidine or control group using a random number
table. The surface of syringe was covered with a tinfoil paper
and numbered by order on the surface. All of the participants
were blinded to grouping, including patients, anesthesiologists
who performed general anesthesia throughout the operations,
and anesthesiologists who set up all the monitors, started the
infusion of syringe medications, and recorded all data.
Patients in the dexmedetomidine group received a loading
dose of dexmedetomidine (0.8 mg$kg1 over 10 min), followed
by continuous infusion of dexmedetomidine (0.4 mg$kg1$h1)
until pneumatic tourniquet deflation. Patients in the control
group received an equal amount of 0.9% saline instead.
Loading of dexmedetomidine or 0.9% saline started immedi-
ately after stable anesthesia status (i.e., a BIS index of 40e45)
was achieved. After the beginning of dexmedetomidine
or saline infusion, lower limb pneumatic tourniquet was
applied at the high thigh level. We determined tourniquet
inflation pressure based on the patient’s SAP, i.e., no less than
twice the patient’s SAP. The range of inflation pressure was
300e350 mm Hg.
We measured HR, SAP, MAP, DAP, and RPP at the following
time points: immediately before dexmedetomidine (or saline)
loading (Tdose), immediately before tourniquet inflation
(Tinflat), every 15 min during tourniquet inflation (T15, T30, T45,
T60, T75, and T90, respectively), and 5 min after tourniquet
e101
deflation (Tdeflat). In addition, we measured CO and SV at Tdose,
T30, T60, T90, and Tdeflat.
Patients who experienced hypertension (i.e., SAP > 160
mm Hg and/or DAP > 90 mm Hg for more than 5 min) during
the experiment were treated with nicardipine injection (5 mg,
IV, every 5 min). Patients who experienced hypotension (i.e.,
SAP < 90 mm Hg and/or MAP < 70 mm Hg for more than 5 min)
were treated with incremental doses of ephedrine injection
(i.e., 4, 8, 10, 12, 14, and 16 mg, IV). Tachycardia (i.e., HR > 100
beats$min1 for more than 5 min) was treated with esmolol
injection (5 mg, IV), whereas bradycardia (i.e., HR < 60
beats$min1 for more than 5 min) was treated with atropine
injection (0.4 mg, IV).
2.5. Statistical analysis
We performed statistical analyses using a commercial soft-
ware package (SPSS 11.5 for Windows; SPSS Science, Chicago,
IL). Data are presented as means with standard deviations.
We examined differences between groups using Student’s
t-test for continuous data and the Chi-square test for cate-
gorical data. We performed repeated-measures analysis of
variance with Bonferroni corrections to examine the within-
subjects (time) effect, between-subjects (group) effect, and
group by time interaction effect in hemodynamic data. A two-
tailed alpha level of 0.05 was set for all statistical tests, and
P < 0.05 was considered statistically significant. The
percentages of patients who developed tourniquet-induced
hyperdynamic response, defined as more than a 30%
increase in SAP during tourniquet inflation [2], were
compared between groups.
3. Results
The demographic data and duration of tourniquet inflation
were comparable between groups (Table 1). The incidence
of tourniquet-induced hyperdynamic response in the control
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Table 1 e Demographic data, types of surgeries, and duration of tourniquet inflation.

Control Dexmedetomidine
group (n ¼ 36) group (n ¼ 36)

Age (y) 43  19 45  18
Gender (M/F) 19/18 12/24
ASA physical status (I/II) 22/14 25/11
Weight (kg) 65  10 70  12
Height (cm) 164  9 166  9
BMI (kg.m2) 24  4 25  4
Type of surgery (TKR/arthroscopy/ORIF) 8/11/17 8/10/18
Tourniquet time (min) 104  22 108  25

ASA ¼ american society of anesthesiologists; TKR ¼ total knee replacement; ORIF ¼ open reduction and internal fixation of lower limb.
Values are means  standard deviations.

group was significantly higher than that in the dexmedeto-
midine group (67.6% versus 19.4%; P < 0.001) (Table 2).
However, the total doses of nicardipine and atropine
consumption in these two groups were comparable (Table 2).
In contrast, the total dose of ephedrine consumption in the
dexmedetomidine group was significantly higher than that in
the control group (P ¼ 0.020) (Table 2). In addition, none of the
cases included in this study received esmolol.
The baseline hemodynamic data (i.e., HR, SAP, MAP, DAP, CO,
and SV) were comparable between groups. Anesthesia induc-
tion and tracheal intubation exerted similar hemodynamic
effects in both groups, as the HR, SAP, MAP, and DAP values
measured at Tdose of the groups were comparable (Fig. 2 AeD ).
The HR value in the dexmedetomidine group measured at Tinflat
was significantly lower than that measured at Tdose (P < 0.001)
(Fig. 2A), which indicates that dexmedetomidine loading caused
a significant decrease in HR. In contrast, the SAP, MAP, and DAP
values in the dexmedetomidine group measured at Tinflat were
comparable to those measured at Tdose (Fig. 2BeD).
significant increases in SAP in the control group, as the SAP
values of the control group measured at T15, T30, T45, T60, T75,
and T90 were significantly higher than that measured at Tinflat
(all P < 0.001) (Fig. 2B). The SAP value in the control group
measured at Tdeflat was also significantly higher than that
measured at Tinflat (P < 0.001) (Fig. 2B). The SAP values in the
dexmedetomidine group measured at T15, T30, and T45 were
significantly lower than those in the control group (all P <
0.040) (Fig. 2B), which indicates that dexmedetomidine
attenuated the tourniquet-induced SAP increases. However,
the SAP values in the dexmedetomidine group measured at
T60, T75, and T90 were comparable to those in the control group
(Fig. 2B). In contrast, the SAP value in the dexmedetomidine
group measured at Tdeflat was significantly lower than that in
the control group (P < 0.001) (Fig. 2B). The changes in MAP
(Fig. 2C) and DAP (Fig. 2D) paralleled those of SAP (Fig. 2B).
3.3. Dexmedetomidine attenuated tourniquet-induced
increases in RPP

3.1. Dexmedetomidine attenuated tourniquet-induced Repeated-measures analysis of variance revealed that the
increases in HR magnitude of changes in RPP was significantly different
between groups (P < 0.001). Tourniquet inflation also caused
Repeated-measures analysis of variance revealed that the trend significant increases in RPP in the control group, as the RPP
of HR was significantly different between groups (P < 0.001). values measured at T15, T30, T45, T60, T75, and T90 were signifi-
Tourniquet inflation caused significant increases in HR in the cantly higher than that measured at Tinflat (all P < 0.050)
control group, as the HR values measured at T15, T30, T45, T60, T75,
and T90 were significantly higher than that measured at Tinflat (all
P < 0.001) (Fig. 2A). The HR value in the control group measured at
Tdeflat was also significantly higher than that measured at Tinflat Table 2 e Incidence of tourniquet-induced hyperdynamic
response and total consumption of the rescue
(P < 0.001) (Fig. 2A). In contrast, the HR values in the dexmede-
medications.
tomidine group were significantly lower than those in the control
Group P
group throughout the experiment (all P < 0.05) (Fig. 2A), which
value
indicates that dexmedetomidine attenuated the effects of tour- Control Dexmedetomidine
niquet inflation on inducing HR increases. (n ¼ 36) (n ¼ 36)

Tourniquet- 24/12 7/29 <.001a

3.2. Dexmedetomidine attenuated tourniquet-induced induced
increases in SAP, MAP, and DAP hyperdynamic
response (Y/N)
Nicardipine (mg) 0.4  1.6 0.1  0.3 .070
Repeated-measures analysis of variance revealed significant Ephedrine (mg) 0.8  3.7 3.6  5.8 .020*
group by time interaction effects in SAP, MAP, and DAP, which Atropine (mg) 0.03  0.12 0.08  0.17 .230
indicates that the magnitude of the changes in SAP, MAP, and
Values are means  standard deviations.
DAP were significantly different between groups (P ¼ 0.002, a
P < .050, dexmedetomidine versus control group.
0.042, and 0.012, respectively). Tourniquet inflation caused
 j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 9 ( 2 0 1 3 ) e 9 9 ee 1 0 6 e103

Fig. 2 e Changes in (A) HR, (B) SAP, (C) MAP, (D) DAP, and (E) RPP. We measured HR, SAP, MAP, DAP, and RPP at the following
time points: immediately before dexmedetomidine (or saline) loading (Tdose), immediately before tourniquet inflation
(Tinflat), every 15 min during tourniquet inflation (T15, T30, T45, T60, T75, and T90, respectively), and 5 min after tourniquet
deflation (Tdeflat). Data are represented as means and standard deviations. Dex [ dexmedetomidine (or saline) loading;
Inf [ tourniquet inflation; Def [ tourniquet deflation. *P < 0.05, dexmedetomidine group versus control group. yP < 0.05,
Tinflat versus Tdose. #P < 0.05 versus Tinflat.

(Fig. 2E). The RPP value measured at Tdeflat was also significantly
higher than that measured at Tinflat (P < 0.001) (Fig. 2E). Similar
to HR, the RPP values in the dexmedetomidine group measured
during and after tourniquet deflation were significantly lower
than those in the control group (all P < 0.010) (Fig. 2E).
3.4. Dexmedetomidine attenuated tourniquet-induced
increases in CO
Repeated-measures analysis of variance revealed that the
magnitude of changes in CO was significantly different
between groups (P ¼ 0.001). The CO values in the control group
measured at T30, T60, T90, and Tdeflat were significantly higher
than those measured at Tdose (all P < 0.035) (Fig. 3A). The CO
values in the dexmedetomidine group measured at T30, T60, T90,
and Tdeflat were significantly lower than those in the control
group (all P < 0.010) (Fig. 3A). In contrast to CO, the difference in
the pattern of changes in SV between groups was not statisti-
cally significant (P ¼ 0.511). The SV values in the two groups
were comparable throughout the experiment (Fig. 3B).
4. Discussion
Data from this study confirmed that tourniquet inflation in-
duced a hyperdynamic response in general anesthesia patients
undergoing lower limb orthopedic surgery. As mentioned ear-
lier, an augmented sympathetic outflow has been proposed
to be an essential mechanism contributing to this tourniquet-
induced hyperdynamic response [4,5]. Dexmedetomidine sti-
mulates the central presynaptic a2A-adrenergic receptors and
exerts central sympatholytic effects that can significantly
decrease the plasma concentrations of norepinephrine and
epinephrine [10e12]. Judging from these data, we thus
hypothesized that dexmedetomidine could attenuate the
tourniquet-induced hyperdynamic response. Data from this
study confirmed our hypothesis. In concert with clinical data
observed in three patients requiring tourniquet for surgery [13],
our data provide clear evidence to support the concept that
dexmedetomidine can serve as an effective adjunct to general
anesthesia in patients using pneumatic tourniquet for lower
limb surgery. Because the tourniquet-induced hyperdynamic
response is resistant to therapies [3], data from this study thus
should have certain clinical significance and warrant further
investigations.
Our data confirmed the effects of dexmedetomidine on
mitigating the tourniquet-induced hyperdynamic response in
general anesthesia patients; nevertheless, they also revealed
that the efficacy of dexmedetomidine on attenuating the
tourniquet-induced hyperdynamic response was gradually
decreased in the delayed phase of tourniquet inflation. Mech-
anisms underlying this observation remain to be elucidated.
e104 j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 9 ( 2 0 1 3 ) e 9 9 ee 1 0 6
Fig. 3 e Changes in (A) CO and (B) SV. We measured CO and SV at the following time points: immediately before
dexmedetomidine (or saline) loading (Tdose), every 30 min during tourniquet inflation (T30, T60, and T90, respectively), and
5 min after tourniquet deflation (Tdeflat). Data are represented as means and standard deviations. Dex [ dexmedetomidine
(or saline) loading. Other abbreviations and symbols as in Fig. 2.
However, judging from the time course, we speculate that the
gradual decrease in the efficacy of dexmedetomidine might be
related to the continuous increases in plasma concentrations
of epinephrine and norepinephrine induced by prolonged
tourniquet inflation [5]. If so, a gradual increase in the dosage of
dexmedetomidine infusion rather than a fixed-dosage infu-
sion in the delayed phase of tourniquet inflation should be
considered to achieve better hemodynamic control.
Among the hemodynamic parameters investigated, our
data revealed that dexmedetomidine exerted sustained effects
on mitigating tourniquet-induced increases in HR, RPP, and
CO. Because dexmedetomidine posed no significant effects on
mitigating tourniquet-induced increases in SV, our data
suggest that the sustained effects of dexmedetomidine on RPP
and CO may result mainly from to its HR-decreasing effect.
Dexmedetomidine was reported to induce significant HR and
blood pressure decreases in conscious healthy volunteers
through a central sympatholytic mechanism [10,11]. During
initial infusion, however, dexmedetomidine could stimulate
the peripheral postsynaptic a2B-adrenergic receptors and
induce an immediate blood pressure increase and reflex HR
decreases in conscious healthy volunteers [10,11]. This effect
was not observed in general anesthesia patients [14,15]. In
contrast, an immediate HR decrease and relatively stable blood
pressure in general anesthesia patients during initial infusion
of dexmedetomidine was reported [14,15]. We observed similar
results in this study. The discrepancy between conscious and
anesthetized patients was postulated to involve the vasodila-
tation effects of anesthetics (e.g., sevoflurane) and the syner-
gistic negative chronotropic effects of dexmedetomidine and
anesthetics [14,15].
Previous data indicated that patients with fewer perioper-
ative hemodynamic fluctuations had lower postoperative
mortality [16,17]. To maintain perioperative hemodynamic
stability, in this study we treated patients who developed
hypertension, hypotension, tachycardia, or bradycardia with
medications including nicardipine, ephedrine, esmolol, and
atropine, respectively. The total consumption of nicardipine,
esmolol, and atropine was comparable in these two groups.
However, the total ephedrine consumption was significantly
higher in the dexmedetomidine group, which mostly
happened between dexmedetomidine loading and tourniquet
inflation. These data indicate that the incidence of perioper-
ative hypotension was higher in the dexmedetomidine group.
We determined the loading dose of dexmedetomidine
according to previous data showing that a loading dexmede-
tomidine infusion of 1 mg$kg1 over 10 min followed by
a maintenance infusion rate of 0.2e0.7 mg$kg1$h1 could
provide effective sedation for intensive care unit patients [18].
Because patients in this study also received sedative and
anesthetic agents (i.e., midazolam, fentanyl, propofol, and
sevoflurane), we decided to adjust the loading dose of dex-
medetomidine to 0.8 mg$kg1$h1 to minimize the hemody-
namic effects of dexmedetomidine. However, judging from
our data revealing that dexmedetomidine loading caused
bradycardia and hypotension, we believe that the loading
dose of dexmedetomidine should be lowered.
Similar to dexmedetomidine, the widely used a2-agonist
clonidine has also been shown to effectively attenuate
tourniquet-induced hyperdynamic response in general anes-
thesia patients [5,19]. Those data [5,19], in concert with data
from the present study, confirmed the concept that incorpo-
rating a2-adrenergic receptor agonist (either dexmedetomi-
dine or clonidine) in general anesthesia patients requiring
tourniquet for surgery is beneficial. However, the question
remains unstudied whether one of the a2-adrenergic receptor
agonists is superior to the other regarding the efficacy or safety
in mitigating a tourniquet-induced hyperdynamic response in
general anesthesia patients. More studies are needed before
further conclusions can be drawn.
Certain study limitations exist. First, the interval between
dexmedetomidine loading and tourniquet inflation varied
between cases. This factor should be taken into consideration
should further data interpretation be intended regarding the
effect and safety of dexmedetomidine. Second, we employed
only one infusion protocol of dexmedetomidine in this study.
The ideal infusion protocols and ideal dosages of dexmedeto-
midine in this regard remain to be elucidated. Third, although
 j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 9 ( 2 0 1 3 ) e 9 9 ee 1 0 6
the between-group difference regarding the types of surgery
was not statistically significant, the types of surgery within
group were heterogeneous in our study. Therefore, the impact
of this factor should be taken into consideration for further
data interpretation. Fourth, this study included only healthy
adult patients, to avoid possible confounding factors. For
instance, this study chose to exclude patients with a history of
hypertension, cardiac arrhythmia, congestive heart failure,
diabetes mellitus, and renal dysfunction. It also chose to
exclude obese patients, because obesity is closely related to
diseases such as hypertension, heart disease, diabetes melli-
tus, endothelial dysfunction, sleep apnea, and chronic kidney
disease [20,21]. Therefore, it might not be possible to extrapo-
late results from this study to those patients. Fifth, as
mentioned earlier, the tourniquet-induced hyperdynamic
response is associated with augmented sympathetic outflow
[4]. Previous data further indicate that augmented sympathetic
outflow would increase energy expenditure and impose
adverse effects on vital organs including the heart, lungs, and
kidney, if the increased energy expenditure persisted [22].
Although we did not measure basal energy expenditure,
previous data indicated that it has a strong correlation with
minute ventilation and heart rate [23]. Because we conducted
minute ventilation in a preprogrammed style in this study, we
did not expect to observe significant between-group differ-
ences in this regard. However, our data revealed that subjects
receiving dexmedetomidine had a lower heart rate than did
those who received saline. Judging from these data, we thus
speculate that basal energy expenditure in patients in the
dexmedetomidine group was lower than for those in the
control group. Sixth, dexmedetomidine can work synergisti-
cally with sevoflurane, because previous data indicated a 17%
decrease in the minimal alveolar concentration of sevoflurane
in adult patients with 0.7-ng$mL1 target dexmedetomidine
plasma concentration [24]. According to the STANPUMP
computer program, the loading dose of dexmedetomidine
employed in this study (i.e., 0.8 mg$kg1 over 10 min) may have
resulted in the target plasma concentration of 0.7e0.95
ng$mL1 in our patients. Therefore, it is possible that dexme-
detomidine loading could decrease the BIS index level and
subsequently cause anesthesiologists to turn down sevo-
flurane to maintain a BIS index of 40e45. Moreover, this might,
in turn, limit the blinding of the anesthesiologists. If so, this
possibility should be taken into account if further data inter-
pretation is intended.
In conclusion, dexmedetomidine attenuates tourniquet-
induced hyperdynamic response in general anesthesia patients
undergoing lower limb surgeries.
Acknowledgments
The authors thank Dr. Mei-Chi Lin and Ms. Huy-Fang Wang for
technical support. They also thank Mr. Yen-Chun Fan for
statistical support. This work was mainly conducted at
Mackay Memorial Hospital and was supported by grants from
the Mackay Memorial Hospital (MMH 9729) and the National
Science Council, Taiwan (NSC 96-2314-B-195-004-MY3),
awarded to HCL and CJH, respectively.
e105
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