Journal of Clinical Anesthesia (2008) 20, 431–436

Original contribution

The effects of preanesthetic, single-dose dexmedetomidine

on induction, hemodynamic, and cardiovascular parameters
Hülya Basar MD (Associate Professor)a,⁎, Serpil Akpinar MD (Resident)b ,
Nur Doganci MD (Resident)b , Unase Buyukkocak MD (Associate Professor)b ,
Çetin Kaymak MD, PhD (Associate Professor)b , Ozgur Sert MD (Resident)b ,
Alpaslan Apan MD (Associate Professor)b
a
Department of Anesthesiology and Reanimation, Ministry of Health, Ankara Training and
Education Hospital, Ankara, 06340 Turkey
b
Department of Anesthesiology and Reanimation, School of Medicine, University of Kırıkkale, Kırıkkale, 71100 Turkey

Received 7 September 2006; revised 10 April 2008; accepted 16 April 2008

Keywords: Abstract
Dexmedetomidine;
Study Objectives: To investigate the hemodynamic, cardiovascular, and recovery effects of
Single dose;
dexmedetomidine used as a single preanesthetic dose.
Preanesthetic dose
Design: Randomized, prospective, double-blind study.
Setting: University Hospital of Kirikkale, Kirikkale, Turkey.
Patients: 40 ASA physical status I and II patients, aged 20 to 60 years, who were scheduled for elective
cholecystectomy.
Interventions: Patients were randomly divided into two groups to receive 0.5 μg kg−1
dexmedetomidine (group D, n = 20) or saline solution (group C, n = 20). Anesthesia was induced
with thiopental sodium and vecuronium, and anesthesia was maintained with 4% to 6% desflurane.
Measurements: Mean arterial pressure (MAP), heart rate (HR), ejection fraction (EF), end-diastolic
index (EDI), cardiac index (CI), and stroke volume index (SVI) were recorded at 10-minute intervals.
The times for patients to “open eyes on verbal command” and postoperative Aldrete recovery scores
were also recorded.
Main Results: In group C, an increase in HR and MAP occurred after endotracheal intubation. In group
D, HR significantly decreased after dexmedetomidine was given. The EDI, CI, SVI, and EF values were
similar in groups D and C. The modified Aldrete recovery scores of patients in the recovery room were
similar in groups C and D at the 15th minute.
Conclusions: A single dose of dexmedetomidine given before induction of anesthesia decreased
thiopental requirements without serious hemodynamic effects or any effect on recovery time.
Crown Copyright © 2008 Published by Elsevier Inc. All rights reserved.

⁎ Corresponding author. Tel.: +90 595 3180; fax: +90 5953652.

E-mail address: hulya_basar@yahoo.com (H. Basar).

0952-8180/$ – see front matter Crown Copyright © 2008 Published by Elsevier Inc. All rights reserved.
doi:10.1016/j.jclinane.2008.04.007
432
1. Introduction
Dexmedetomidine is an α2 adrenergic receptor agonist
with high selectivity for the α2 receptor. The α2 adrenergic
mechanism causes dose-dependent reductions in blood
pressure (BP) and heart rate (HR) [1]. Dexmedetomidine
has analgesic, anxiolytic, and sedative effects in the
intensive care unit after intravenous (IV) administration
[2]. The hypnotic response is probably mediated by
activation of the α2 adrenoreceptors. These properties
render dexmedetomidine an ideal preanesthetic medication
for surgical procedures.
The α2 agonists, including clonidine and dexmedetomi-
dine, decrease central sympathetic outflow and modify
intraoperative cardiovascular responses to surgical stimuli
and laryngoscopy. The reduction in tachycardia, hyperten-
sion, and sympathetic activity may be of benefit in patients
at risk of myocardial ischemia [3]. Various studies have
shown the sedative and hemodynamic effects of a single
0.5 μg kg−1 dose for dilatation and curettage [4]. How-
ever, little if any information has been published on the
effect of a single dose of dexmedetomidine on cardiac and
recovery parameters.
The purpose of this study was to investigate the effects of
a single IV dose of dexmedetomidine administered 10 min-
utes before induction of anesthesia on thiopental sodium
requirements, hemodynamics, and recovery parameters in
patients undergoing elective cholecystectomy.
2. Materials and methods
With approval from the University Hospital of Kirikka-
le's research ethics committee and after obtaining patients'
written, informed consent, we enrolled into the study 40
ASA physical status I and II patients, aged 20 to 60 years,
who were scheduled for elective cholecystectomy (Group
C: control group; Group D: dexmedetomidine group).
Exclusion criteria included patients with a history of
alcohol abuse or cardiac, pulmonary, hepatic, or renal
disease. On the study day, all patients were premedicated
with atropine intramuscularly 45 minutes before induction
of anesthesia. Heart rate, peripheral oxygen saturation,
noninvasive mean arterial pressure (MAP), and end-tidal
carbon dioxide were monitored continuously until extuba-
tion. In addition, electrodes for the measurement of cardiac
index (CI) by thoracic bioimpedance were positioned on
each subject according to methods described by the
manufacturer (model NCCOM-3R7, BoMed Medical
Manufacturing Ltd, Irvine, CA).
After baseline parameters were noted, patients were
allocated randomly to the two groups using a computer-
generated random numbers table. An anesthesiologist who
was not one of the study participants prepared syringes
containing either dexmedetomidine or 0.9% saline. Both
H. Basar et al.
syringes were labeled “study drug” and coded to maintain
the double-blinded nature of the study. Dexmedetomidine
0.5 μg kg−1 was prepared in a 10-mL isotonic solution.
A 10-mL isotonic solution was also prepared for the control
group. Dexmedetomidine was administered by slow IV push
(over 60 sec) 10 minutes before anesthesia. After recording
bispectral index (BIS) values, anesthesia was induced with
thiopental sodium until loss-of-eyelid reflex. The dosage of
thiopental was recorded. Vecuronium 0.1 mg kg−1 was used
for neuromuscular relaxation. Anesthesia was maintained
with desflurane in nitrous oxide/oxygen 50:50 mixture,
titrated to achieve a BIS value between 40 and 60. Controlled
mechanical ventilation was adjusted to maintain end-tidal
carbon dioxide between 34 and 45 mmHg. Ejection fraction
(EF), end-diastolic index (EDI), CI, and stroke volume index
(SVI) were recorded by noninvasive thoracic electrical
bioimpedance for baseline, after dexmedetomidine-saline
injection (pretreatment), at thiopental sodium administration,
intubation, and at 10-minute intervals. No opioids were
used intraoperatively.
At the time of the last suture, the desflurane and nitrous
oxide were turned off, and 100% oxygen was administered.
Neuromuscular block was antagonized with neostigmine
(0.04 mg kg−1) and atropine (0.15 mg kg−1). Thereafter, the
times for patients to “open eyes on verbal command” were
recorded. Recovery from anesthesia was assessed by
modified Aldrete recovery score.
Statistical analyses were performed using SPSS for
Windows 8.0 (SPSS Inc, Chicago, IL). The sample size
was determined by power analysis [5]. A sample size of 19
patients per group was required to detect a 20% change in
HR, MAP, and other cardiovascular variables (CI, EF, SVI,
and EDI) between baseline and intubation time, with a power
of 80% at the 5% significance level.
Data are reported as means ± standard deviation. A
P value b0.05 was accepted as statistically significant.
Statistical analysis of demographic data, BIS values, and
hemodynamic and cardiovascular values were analyzed
using Student's t test between groups.
Dependent variables of hemodynamic and cardiovascu-
lar parameters for each measure were analyzed with
repeated measures analysis of variance and post hoc
Bonferroni correction.
3. Results
The groups were similar in patient and operative
characteristics (Table 1). Ten minutes after, the preanes-
thetic single dose of dexmedetomidine or saline was
given, the BIS value was 95 ± 10 in Group C and 87 ± 1
in Group D (P = 0.001).
There was a significant decrease in dose of thiopental
for loss-of-eyelid reflex during induction of anesthesia
(518 ± 62 mg for Group C, 354 ± 72 mg for Group D;
P b 0.000).
Use of preanesthetic dexmedetomidine 433

Table 1 Demographic characteristics of the study patients and

average duration of surgery
Group C Group D P
(control) (dexmedetomidine)
Age (yrs) 45.72 ± 16.54 43.22 ± 16.2 0.471
Weight (kg) 68.6 ± 10.37 71.44 ± 14.68 0.215
Height (cm) 162 ± 5.05 166.16 ± 8.62 0.196
Gender 12/8 9/11 0.504
(male/female)
BSA (m2) 1.88 ± 0.1 1.81 ± 0.11 0.632
Duration of 85 ± 13 79 ± 20 0.481
anesthesia (min)
BSA = body surface area.
Fig. 2 Heart rate (HR) course of Group C (control) and Group D
(dexmedetomidine). *Significant difference between Groups C and
D after intubation (P = 0.024) and on the 10th minute (P = 0.013).
Among the hemodynamic parameters, HR was sig- &
P = 0.003; significant increase in Group C after intubation versus
nificantly low only at the 10th minute (P = 0.024) and baseline. #P = 0.000; significant decrease noted in Group D after
MAP (P = 0.026), at the 30th minute for Group D versus dexmedetomidine administration versus baseline.
Group C (Figs. 1 and 2). Within-group evaluation showed
that HR (P = 0.003) and MAP (P = 0.002) increased There was a significant decrease only in CI after dexmede-
significantly compared with baseline values in Group C. tomidine administration in Group D versus the baseline value
There were no differences at other intraoperative stages. In (P = 0.009), whereas other parameters also tended to
Group D, there was a significant decrease in MAP at the 10th decrease during surgery.
minute over baseline (P = 0.001), whereas HR showed a There were no significant differences in “time to open
significant decrease after dexmedetomidine administration eyes on verbal command” (Groups C and D: 8.7 ± 0.4 and
(P b 0.001). There were no differences during other intra- 8.3 ± 0.6 min, respectively; P = 0.098). Modified Aldrete
operative stages. recovery scores of patients in the recovery room were
There were no differences between the two groups in CI, similar in Groups C and D at the 15th minute, with scores
EF, EDI, or SVI (Tables 2 and 3). Within-group evaluation of 9 ± 1 and 9, respectively (P = 0.132).
showed that EF decreased only on the 20th minute in the
control group compared with the baseline value (P = 0.016),
whereas CI, SVI, and EDI decreased throughout surgery. 4. Discussion

Single-dose 0.5 μg kg−1 preoperative dexmedetomidine

Fig. 1 Mean arterial pressure (MAP) course in Group C (control)
and Group D (dexmedetomidine). *P = 0.026; significant difference
between Groups C and D noted at the 30th minute. &P = 0.002;
significant increase in Group C noted following intubation versus
baseline. #P = 0.001; significant decrease in Group D at the 10th
minute versus baseline.
administration caused significant sedation, decreased the
induction dose of thiopental markedly, and did not cause any
major hemodynamic changes after intubation or during the
intraoperative periods.
The sedative properties of the α2-agonists are well
documented. The hypnotic and sedative actions of dexme-
detomidine are thought to be mediated primarily by
postsynaptic α2-adrenergic receptors. These effects differ
depending on receptor location; in the locus ceruleus, this
stimulation provides sedation [6]. In healthy volunteers, IV
dexmedetomidine 0.5 to one μg kg−1 caused sedation within
5 minutes and reached maximum effects at 15 minutes [7].
The BIS monitor quantifies anesthetic effects on the brain
and, specifically, the hypnotic component. In our study, we
found a borderline range of sedation (70-89) for BIS values
10 minutes after administration of 0.5 μg kg−1 dexmedeto-
midine in contrast to the control group.
The induction dose of thiopental sodium was significantly
lower (37%) than the placebo group after administration of
0.5 μg kg−1 single-dose dexmedetomidine [4]. Dutta et al [8]
showed that when propofol, another induction agent, was
 434
Table 2 Group C cardiovascular parameters
Group C Baseline Pretreatment Intubation 10 min 20 min 30 min 40 min 50 min 60 min 70 min 80 min Extubation
(saline)
CI 3.24 ± 0.7 2.52 ± 0.6 2.55 ± 0.6 2.23 ± 0.7 2.28 ± 0.5 2.18 ± 0.4 2.1 ± 0.7 2.87 ± 0.7 2.23 ± 0.8 2.1 ± 0.7 2.23 ± 0.9 2.7 ± 0.5
(Lmin/m2)
EF (%) 52.94 ± 8.8 51.5 ± 4.8 51.66 ± 5.7 49.16 ± 7.8 47.11 ± 9.1 ⁎ 50.72 ± 9.5 50.44 ± 8.8 50.66 ± 10 51.47 ± 8.9 51.06 ± 7.5 53.91 ± 6.5 54.27 ± 10.1
EDI 77.6 ± 14 74.6 ± 13.5 67 ± 12.9 68.6 ± 12.7 64.3 ± 11 65.9 ± 11.6 67 ± 11.4 65.9 ± 14 59.5 ± 12.6 54.2 ± 13 60.1 ± 14.3 64.6 ± 13.5
(mL/m2)
SVI 42.5 ± 10.2 40.2 ± 10.1 31.9 ± 11 31.9 ± 10.8 29.2 ± 11 31.3 ± 11.4 30.8 ± 12 31.9 ± 10.8 30.3 ± 12.1 30.3 ± 9.2 30.8 ± 10.3 32.7 ± 10.2
(mL/m2)
CI = cardiac index; EF = ejection fraction; EDI = end-diastolic index; SVI = stroke volume index.
⁎ P = 0.016; significant decrease versus baseline value.

Table 3 Group D cardiovascular parameters

Group D Baseline Pretreatment Intubation 10 min 20min 30 min 40 min 50 min 60 min 70 min 80 min Extubation
(dexmed)
CI 2.9 ± 0.6 2.09 ± 0.6 ⁎ 2.40 ± 0.7 2.4 ± 0.5 3.2 ± 0.6 2.32 ± 0.6 2.37 ± 0.6 2.37 ± 0.5 2.26 ± 0.7 2.15 ± 0.8 2.32 ± 0.8 2.7 ± 0.7
(L/min/m2)
EF (%) 55.16 ± 9.1 50.1 ± 7.6 49.22 ± 6.9 48.5 ± 5 48.11 ± 8.6 48.38 ± 8.5 48.94 ± 10.1 50.37 ± 9. 51.5 ± 12.3 51.81 ± 12.5 49.77 ± 12.9 50.27 ± 8.1
EDI 69.06 ± 12.8 61.2 ± 10.3 58.09 ± 10.5 60.8 ± 11 62.6 ± 9.5 62.6 ± 12.4 64.08 ± 11.7 60 ± 13 58.01 ± 12.5 61.1 ± 12.1 60.7 ± 12.3 62.9 ± 11
(mL/m2)
SVI 37.6 ± 11.2 32.3 ± 12.4 30.5 ± 10.8 30.1 ± 13 31.1 ± 12.9 29.9 ± 12 33.3 ± 11.3 31.36 ± 13.1 30.5 ± 11.3 32.5 ± 13.1 32.3 ± 11 23.3 ± 12.3
(mL/m2)
CI = cardiac index; EF = ejection fraction; EDI = end-diastolic index; SVI = stroke volume index.

H. Basar et al.
⁎ P = 0.009; significant decrease versus baseline value.
Use of preanesthetic dexmedetomidine
used, dexmedetomidine decreased the propofol concentra-
tion necessary for sedation by approximately 60% to 80%;
Aho et al [9] found that opioid requirement decreases
following 0.4 μg kg−1 dexmedetomidine. Plasma noradrena-
line concentration was markedly reduced in patients
receiving dexmedetomidine. This decrement in neuronal
noradrenaline release may explain in part the reduction in
thiopental requirements [4]. The response to thiopental is
shown by three clinical signs: loss of eyelid reflex, loss of
corneal reflex, and absence of movement in response to
squeezing the trapezius muscle. The eyelid reflex was lost at
significantly lower levels of thiopental than the corneal or
movement response [10].
The use of α2 agonists in the preoperative period has been
associated with attenuated HR and BP responses to stressful
events. The presence of an endotracheal tube leads to reflex
sympathetic responses during both intubation and extuba-
tion. Sympathetic responses include hypertension, tachycar-
dia, increased intraocular and intracranial pressures,
bronchospasm, and myocardial ischemia. Jaakola et al [11]
showed that dexmedetomidine attenuated the increase in HR
and BP during intubation. Lawrence et al [12] found that a
single dose of dexmedetomidine before induction of
anesthesia attenuated the hemodynamic response to intuba-
tion and extubation. They used a large dose (two μg kg−1) of
dexmedetomidine; bradycardia was observed on the first and
fifth minutes after administration [12]. Unlugenc et al [13]
gave one μg kg −1 dose of dexmedetomidine within
10 minutes of induction, and they found a marked decrease
in HR within 10 minutes, whereas HR and MAP were similar
to values seen in the other group during surgery. Bloor et al
[14] used 4 different doses during their study, with the small
doses defined as 0.25 and 0.5 μg kg−1. In our study, there
was a 21.7% increase in MAP and 21.7% increase in HR
compared with baseline values in the control group, whereas
there was no hemodynamic response to intubation in
Group D. Mean arterial pressure and HR were similar in
the two groups during surgery.
The hypotensive and bradycardic effects of dexmedeto-
midine, as with other α2 agonists, are the result of the drug's
actions on several brainstem and medullary nuclei (including
nucleus tractus solitarus and the lateral reticular nucleus) and
the hypothalamus to decrease sympathetic nervous activity.
We found that MAP showed a significant decrease compared
with the control group only at the 50th minute. The study of
Kallio et al [15] found that the hypotensive effect of
dexmedetomidine reached its maximum (18%) between 60
and 120 minutes after a 75 μg bolus administration.
Temporary bradycardia, especially between 0 and 15 minutes
after administration of 50 and 75 μg, has been noted. We
might have observed more marked effects with similar
dosages because there was no surgical stress factor in our
study. We observed only a bradycardic response in Group D
after dexmedetomidine infusion. After administration of
dexmedetomidine, HR response to intubation was almost
completely depressed, and rate pressure product was
435
decreased. Hence, depression of sympathetic response
against intubation is an important advantage, especially in
high-risk patients.
Bloor et al [14] measured cardiac output (CO) with the
bioimpedance method after an infusion dose of dexmede-
tomidine 0.25, 0.5, one, and two μg kg−1 and reported a
decrease of 13%, 12%, and 18% in CO values at the 95th,
150th, and 105th minutes, respectively. Kallio et al [16]
reported a 23% decrease in CO using the Doppler
echocardiographic method after IV administration of
100 μg single-dose medetomidine. The MAP and CO
decrease in values were proportional in the same study. We
detected a decrease in all parameters compared with basal
values at certain periods. We detected only a significant
decrease in CI in Group D after dexmedetomidine
administration (27.9%). The intraoperative course of
cardiac parameters was similar.
The modified Aldrete recovery score at the time the
patients were taken into the recovery room and the time
needed to reach the appropriate recovery level were
similar in the two groups. Unlugenc et al also found
similar recovery times among patients administered a
one μg kg−1 bolus of preoperative dexmedetomidine and
those given a placebo [13]. That study used a different
system of scoring to evaluate their patients and found that
they reached the appropriate recovery level within a mean
duration of 10.3 to 11.7 minutes. The modified Aldrete
recovery score at the 15th minute, when patients were
leaving the recovery room, was 8.76 and 8.65 points in
the two groups.
In conclusion, a single dose of 0.5 μg kg −1 of
dexmedetomidine given preoperatively 10 minutes before
induction led to significant sedation, decreased thiopental
dosage, and blunted hemodynamic response to intubation
with no change in recovery scores.
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