Current Drug Targets, 2009, 10, 687-695687
1389-4501/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd.
Dexmedetomidine Use in General Anaesthesia
A. Arcangeli*, C. D’Alò and R. Gaspari
Institute of Anesthesia and Intensive Care, Catholic University of Rome, Italy
Abstract: Dexmedetomidine is a potent and highly selective ?2-adrenoreceptor agonist currently utilized for continuous
infusion for sedation/analgesia in the intensive care unit (ICU). Dexmedetomidine offers remarkable pharmacological
properties including sedation, anxiolysis, and analgesia with the unique characteristic to cause no respiratory depression.
In addition it posses sympatholytic and antinociceptive effects that allow hemodynamic stability during surgical
stimulation. Different from most of clinically used anesthetics, dexmedetomidine brings about not only a sedative-
hypnotic effect via an action on a single type of receptors, but also an analgesic effect and an autonomic blockade that is
beneficial in cardiac risk situations. Several studies have demonstrated its safety, although bradycardia and hypotension
are the most predictable and frequent side effects.
Dexmedetomidine has shown to consistently reduce opioids, propofol, and benzodiazepines requirements. In the last years
it has emerged as an affective therapeutic drug in a wide range of anesthetic management, promising large benefits in the
perioperative use. In particular this review focuses on dexmedetomidine utilization in premedication, general surgery,
neurosurgery, cardiac surgery, bariatric surgery, and for procedural sedation and awake fiberoptic intubation. In all these
fields dexmedetomidine has demonstrated to be an efficacious and safe adjuvant to other sedative and anesthetic
Keywords: ?2-Adrenoreceptor agonists, dexmedetomidine, sedation, anesthesia, perioperative use.
specific ?2-adrenoreceptor agonist that has both sedative and
analgesic effects. The prototype of ?2-adrenoreceptor agonist
clonidine was initially developed in 1960s as a nasal
decongestant for its locally
vasoconstrictor action, but later in 1966 it was introduced
into the market as a potent antihypertensive drug .
Nowadays the therapeutic use of this class of drugs has
shifted to various other clinical indications including
anxiolysis, analgesia, sedation that render them suitable as
adjuncts in anesthesia. Dexmedetomidine was approved in
the USA in 1999 for sedation and analgesia in the intensive
care unit. Compared with clonidine, dexmedetomidine is
about eight times more specific for ?2-adrenoreceptors with
an ?2: ?1selectivity ratio of 1600 : 1 Fig. (1). These unique
properties of dexmedetomidine make it an ?2-adrenoreceptor
full agonist agent with sedative and anxiolytic effects. The
elimination half-life of dexmedetomidine is approximately 2
hours with a rapid distribution half-life being approximately
6 min [2, 3]. It has a rapid onset of action. It undergoes
biotransformation in the liver, and the kidney excretes 95%
of its metabolites.
Dexmedetomidine is a potent, highly selective and
particularly suitable for intravenous infusion. Although
dexmedetomi-dine is approved for sedation/analgesia in an
intensive care setting, in the last years it has emerged as an
affective therapeutic drug in a wide range of anesthetic
The short half-life of dexmedetomidine makes it
*Address correspondence to this author at the Institute of Anesthesia and
Intensive Care, Catholic University of the Sacred Heart, Largo F. Vito 1,
00013 Rome, Italy; E-mail: firstname.lastname@example.org
Fig. (1). The chemical structure of ?2-adrenoreceptor agonists
clonidine and dexmedetomidine.
?2-adrenoreceptor agonists act at pre- and postsynaptic
adrenoceptors and their pharmacology is complex. The
human ?2-adrenoreceptors can be classified into ?2A, ?2B and
?2C adrenoceptors subtypes. These receptor subtypes are
distributed ubiquitously and each may be responsible for a
specific action of ?2-agonists [4, 5]. The predominant ?2-
adrenoreceptor agonist subtype mediating sedative and
antinociceptive actions is the ?2A-adrenoceptor. Whereas
stimulation of ?2B-adrenoceptor mediates the vasoconstric-
tive cardiovascular effect, which causes the initial
hypertension observed after the administration of ?2-adreno-
receptor agonists [6,7]. The ?2C - adrenoceptors subtype has
688 Current Drug Targets, 2009, Vol. 10, No. 8 Arcangeli et al.
been shown to modulate dopaminergic neurotransmission,
hypothermia and a variety of behavioral responses.
the hyperpolarization of noradrenergic neurons located in the
locus ceruleus . Dexmedetomidine acts through a G-
coupled protein receptor that produces an inhibition of
adenylcyclase and this results in decreased formation of
cyclic AMP (cAMP), that is an important regulator of many
cellular functions acting in various intracellular subsystem
like the control of phosphorilation state of regulatory
proteins. Other effects of ?2-adrenoreceptor agonists include
activation of potassium ion channels causing efflux of
potassium and an inhibition of calcium entry into calcium
channels in neuronal cell . These effects lead to change in
membrane ion conductance and produce ?2-adrenoreceptor
agonist hyperpolarization of the membrane which suppresses
neuronal activity. The main effect is an inhibition of
noradrenalin release causing a reduction of excitation,
especially in locus coeruleus. The locus coeruleus is ?2-
adrenoreceptor agonist small neuronal nucleus located
bilaterally in the upper brainstem and is the ?2-
adrenoreceptor agonist major site of noradrenergic
innervations in the brain . The locus coeruleus has also
been implicated as ?2-adrenoreceptor agonist key modulator
for ?2-adrenoreceptor agonist variety of important brain
functions, including arousal, sleep, anxiety and drug
withdrawal associated with CNS depressant, like opioids.
The hypnotic effect of dexmedetomidine is mediated by
adrenoreceptor agonists show a biphasic, dose-dependent,
blood pressure effect. At low doses the dominant action of
?2-adrenoreceptor agonist activation is a reduction in
sympathetic tone, mediated by a reduction of norepinephrine
release at the neuroeffector junction, and a inhibition of
neurotransmission in sympathetic nerves . The net effect
of dexmedetomidine action is a significant reduction in
circulating catecholamines with a slight decrease in blood
pressure and a modest reduction in heart rate . When
dexmedetomidine is administered as a continuous infusion,
is associated with an expected and stable hemodynamic
response. Significant hypotension is usually only observed in
patients with preexisting hypovolemia or vasoconstriction.
The bradycardia frequently seen after the administration of
dexmedetomidine may be due to the central sympatholytic
action and partly by baroceptor reflex and enhanced vagal
activity. This effect is frequently observed in younger
patients with high levels of vagal tone.
The hemodynamic effects of dexmedetomidine result
peripheral and central mechanism. Alpha2-
hypertensive action caused by the activation of ?2B
adrenoceptors located on vascular smooth muscle cells. This
effect proscribes the rapid intravenous injection of
At higher doses of dexmedetomidine produce an
Respiratory System Effects
ventilation. Although dexmedetomidine produces sedative,
analgesic and anxiolytic affects, unlike other sedatives, it
provides respiratory stability and does not cause ventilator
depression. This was shown in healthy volunteers in whom
The ?2-adrenoreceptor agonists have minimal effects on
even very high doses of dexmedetomidine did not
compromise respiratory function . Absence of respi-
ratory depression was also observed in patients sedated with
dexmedetomidine, which was administered at infusion rates
10 to 15 times higher than maximally recommended . It
was also demonstrated that combination of ?2-adrenoreceptor
agonist with opioids does not lead to further ventilator
Central Nervous System Effects
provides sedation, anxiolysis and analgesia. The sedation
produced by ?2-adrenoreceptor agonists does not depend
primarily on activation of the ?-aminobutyric acid (GABA)
receptors like that produced by traditional sedatives, such as
propofol or benzodiazepines. The primary site of action of
?2-adrenoreceptor agonist is the locus ceruleous and not the
cerebral cortex, as would be the case with GABA-mimetic
drugs . This should be the reason why this class of drugs
produces a different type of sedation compared with
benzodiazepines and propofol.
Dexmedetomidine, like other ?2-adrenoreceptor agonists,
properties, it produces an unusually cooperative form of
sedation in which the patient is calmly and easily roused
from sleep to wakefulness to allow task performance and
excellent communication and cooperation while intubated
and ventilated and then quickly back to sleep when not
stimulated . The unusual subcortical form of
dexmedetomidine induced sedation is characterized by an
easy and quick arousal, resembling natural sleep. With
increasing doses of dexmedetomidine, profound anesthetic
actions have been demonstrated, and this advocates that
dexmedetomidine could be used as total intravenous agent.
The neuroprotective properties of dexmedetomidine have
been demonstrated in various animal models of cerebral
ischemia . There are recent experimental data suggesting
that in addition to ?2-adrenoreceptor agonists, the
neuroprotective effect of dexmedetomidine may include
other pathways in the brain, independent of ?2-
adrenoreceptor agonists and most probably involve I1-
imidazoline receptors in the brainstem and hippocampus
Sedation induced by dexmedetomidine has unique
significant analgesic effects and consistently reduce opioid
requirements . It is believed that the spinal cord is
probably the major site of analgesic action, where the
activation of ?2c-adrenoreceptor agonist subtype seems to
increase the analgesic action of opioids in lowering the
transmission of nociceptive signals to brain centers .
Dexmedetomidine also inhibits the release of substance P
from the dorsal horn of the spinal cord, leading to primary
Dexmedetomidine has been demonstrated to have
Renal System Effects
in diuresis and natriuresis possibly through an ability to
reduce efferent sympathetic outflow of the renal nerve. In
addition dexmedetomidine has shown to decrease the
secretion of vasopressin and to antagonize its effect on renal
Stimulation of ?2-adrenoreceptors in the kidneys results
Dexmedetomidine Use in General Anaesthesia Current Drug Targets, 2009, Vol. 10, No. 8 695
 Unlugenc H, Gunduz M, Guler T, Yagmur O, Isik G. The effect of
pre-anaesthetic administration of intravenous dexmedetomidine on
postoperative pain in patients receiving patient-controlled
morphine. Eur J Anaesthesiol. 2005; 22: 386-91.
Basar H, Akpinar S, Doganci N, Buyukkocak U, Kaymak C, Sert
O, et al. The effects of preanesthetic, single-dose dexmedetomidine
on induction, hemodynamic, and cardiovascular parameters. J Clin
Anesth 2008; 20: 431-6.
Yuen VM, Hui TW, Irwin MG, Yuen MK. A comparison of
intranasal dexmedetomidine and oral midazolam for premedication
in pediatric anesthesia: a double-blinded randomized controlled
trial. Anesth Analg 2008; 106: 1715-21.
Schmidt AP, Valinetti EA, Bandeira D, Bertacchi MF, Simões CM,
Auler JO Jr. Effects of preanesthetic administration of midazolam,
clonidine, or dexmedetomidine on postoperative pain and anxiety
in children. Paediatr Anaesth 2007; 17: 667-74.
Aho M, Erkola O, Kallio A, Scheinin H, Korttila K.
Dexmedetomidine infusion for maintenance of anesthesia in
patients undergoing abdominal hysterectomy. Anesth Analg 1992;
Khan ZP, Munday IT, Jones RM, Thornton C, Mant TG, Amin D.
Effects of dexmedetomidine on isoflurane requirements in healthy
volunteers. 1: Pharmacodynamic and pharmacokinetic interactions.
Br J Anaesth 1999; 83: 372-80.
Ohtani N, Kida K, Shoji K, Yasui Y, Masaki E. Recovery profiles
from dexmedetomidine as a general anesthetic adjuvant in patients
undergoing lower abdominal surgery. Anesth Analg 2008; 107:
Ramsay MA, Luterman DL. Dexmedetomidine as a total
intravenous anesthetic agent. Anesthesiology 2004; 101: 787-90.
Ebert T, Maze M. Dexmedetomidine: another arrow for the
clinician's quiver. Anesthesiology 2004; 101: 568-70.
Wahlander S, Frumento RJ, Wagener G, Saldana-Ferretti B, Joshi
RR, Playford HR, et al. A prospective, double-blind, randomized,
placebo-controlled study of dexmedetomidine as an adjunct to
epidural analgesia after thoracic surgery. J Cardiothorac Vasc
Anesth 2005; 19: 630-5.
Wijeysundera DN, Naik JS, Beattie WS. Alpha-2 adrenergic
agonists to prevent perioperative cardiovascular complications: a
meta-analysis. Am J Med 2003; 114: 742-52.
Jalonen J, Hynynen M, Kuitunen A, Heikkilä H, Perttilä J,
Salmenperä M, et al. Dexmedetomidine as an anesthetic adjunct in
coronary artery bypass grafting. Anesthesiology 1997; 86: 331-45.
But AK, Ozgul U, Erdil F, Gulhas N, Toprak HI, Durmus M, et al.
The effects of pre-operative dexmedetomidine infusion on
hemodynamics in patients with
undergoing mitral valve replacement surgery. Acta Anaesthesiol
Scand 2006; 50: 1207-12.
Mukhtar AM, Obayah EM, Hassona AM. Preliminary experience
with dexmedetomidine in pediatric anesthesia. Anesth Analg 2006;
Chrysostomou C, Beerman L, Shiderly D, Berry D, Morell VO,
Munoz R. Dexmedetomidine: a novel drug for the treatment of
atrial and junctional tachyarrhythmias during the perioperative
period for congenital cardiac surgery: a preliminary study. Anesth
Analg 2008; 107: 1514-22.
Bekker AY, Kaufman B, Samir H, Doyle W. The use of
dexmedetomidine infusion for awake craniotomy. Anesth Analg
2001; 92: 1251-3.
Souter MJ, Rozet I, Ojemann JG, Souter KJ, Holmes MD, Lee L, et
al. Dexmedetomidine sedation during awake craniotomy for
seizure resection: effects on electrocorticography. J Neurosurg
Anesthesiol 2007; 19: 38-44.
Rozet I, Muangman S, Vavilala MS, Lee LA, Souter MJ, Domino
KJ, et al. Clinical experience with dexmedetomidine for
implantation of deep brain stimulators in Parkinson's disease.
Anesth Analg 2006; 103: 224-8.
Bekker AY, Basile J, Gold M, Riles T, Adelman M, Cuff G,
Mathew JP, et al. Dexmedetomidine for awake carotid
endarterectomy: efficacy, hemodynamic profile, and side effects. J
Neurosurg Anesthesiol 2004; 16: 126-35.
Dexmedetomidine as an anaesthetic adjuvant in patients
undergoing intracranial tumour
randomized and placebo-controlled study. Br J Anaesth 2006; 97:
Bekker A, Sturaitis M, Bloom M, Moric M, Golfinos J, Parker E, et
al. The effect of dexmedetomidine on perioperative hemodynamics
in patients undergoing craniotomy. Anesth Analg 2008; 107: 1340-
Koroglu A, Demirbilek S, Teksan H, Sagir O, But AK, Ersoy MO.
Sedative, haemodynamic and respiratory effects of dexmedeto-
midine in children undergoing magnetic resonance imaging
examination: preliminary results. Br J Anaesth 2005; 94: 821-4.
Koroglu A, Teksan H, Sagir O, Yucel A, Toprak HI, Ersoy OM. A
comparison of the sedative, hemodynamic, and respiratory effects
of dexmedetomidine and propofol in children undergoing magnetic
resonance imaging. Anesth Analg 2006; 103: 63-7.
Heard C, Burrows F, Johnson K, Joshi P, Houck J, Lerman J. A
comparison of dexmedetomidine-midazolam with propofol for
maintenance of anesthesia in children undergoing magnetic
resonance imaging. Anesth Analg 2008; 107: 1832-9.
Tosun Z, Akin A, Guler G, Esmaoglu A, Boyaci A.
Dexmedetomidine-ketamine and propofol-ketamine combinations
for anesthesia in spontaneously breathing pediatric patients
undergoing cardiac catheterization. J Cardiothorac Vasc Anesth
2006; 20: 515-9.
Sturaitis MK, Lopez D, Munoz L, Toleikis SC, Tuman KJ. Effect
of dexmedetomidine on brain tissue oxygenation (PtiO2) in patients
undergoing cerebrovascular surgery. Anesth Analg 2004; 98: S139.
Demiraran Y, Korkut E, Tamer A, Yorulmaz I, Kocaman B, Sezen
G, et al. The comparison of dexmedetomidine and midazolam used
for sedation of patients during upper endoscopy: A prospective,
randomized study. Can J Gastroenterol 2007; 21: 25-9.
Jalowiecki P, Rudner R, Gonciarz M, Kawecki P, Petelenz M,
Dziurdzik P. Sole use of dexmedetomidine has limited utility for
conscious sedation during outpatient colonoscopy. Anesthesiology
2005; 103: 269-73.
Bergese SD, Khabiri B, Roberts WD, Howie MB, McSweeney TD,
Gerhardt MA. Dexmedetomidine for conscious sedation in difficult
awake fiberoptic intubation cases. J Clin Anesth 2007; 19: 141-4.
Abdelmalak B, Makary L, Hoban J, Doyle DJ. Dexmedetomidine
as sole sedative for awake intubation in management of the critical
airway. J Clin Anesth 2007; 19: 370-3.
Uzümcügil F, Canbay O, Celebi N, Karagoz AH, Ozgen S.
Comparison of dexmedetomidine-propofol vs. fentanyl-propofol
for laryngeal mask insertion. Eur J Anaesthesiol 2008; 25: 675-80.
) Feld JM, Hoffman WE, Stechert MM, Hoffman IW, Ananda RC.
Fentanyl or dexmedetomidine combined with desflurane for
bariatric surgery. J Clin Anesth 2006; 18: 24-8.
Hofer RE, Sprung J, Sarr MG, Wedel DJ. Anesthesia for a patient
with morbid obesity using dexmedetomidine without narcotics. Can
J Anaesth 2005; 52: 176-80.
Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T,
Griffin J, et al. Dexmedetomidine infusion during laparoscopic
bariatric surgery: the effect on recovery outcome variables. Anesth
Analg 2008; 106: 1741-8.
Kaygusuz K, Gokce G, Gursoy S, Ayan S, Mimaroglu C, Gultekin
Y.A comparison of sedation with dexmedetomidine or propofol
during shockwave lithotripsy: a randomized controlled trial. Anesth
Analg 2008; 106: 114-9.
Alhashemi JA, Kaki AM. Dexmedetomidine in combination with
morphine PCA provides superior analgesia for shockwave
lithotripsy. Can J Anaesth 2004; 51: 342-7.
Taghinia AH, Shapiro FE, Slavin SA. Dexmedetomidine in
aesthetic facial surgery: improving anesthetic safety and efficacy.
Plast Reconstr Surg 2008; 121: 269-76.
Ustün Y, Gündüz M, Erdo?an O, Benlidayi ME. Dexmedetomidine
versus midazolam in outpatient third molar surgery. J Oral
Maxillofac Surg 2006; 64: 1353-8.
PE, Kyttä JV, Randell TT, Aantaa RE.
surgery: a double-blind,
Received: April 02, 2009 Revised: April 09, 2009 Accepted: April 09, 2009