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Abstract
The α2-adrenoceptors (ARs) by virtue of their sedative, analgesic, sympatholytic, anesthetic-sparing and hemodynamic-
stabilizing properties, have been used as an adjunct to local anesthetics for prolongation of effect. Dexmedetomidine a
stereoisomer of medetomidine a highly selective α2-adrenergic receptor (AR) agonist with a relatively high ratio of α2/ α1-activity
(1620:1 as compared to 220:1 for clonidine). It has recently been introduced in anesthesia practice. It is currently being
used for continuous intravenous sedation in the intensive care setting and procedural sedation in nonintubated patients.
Keywords: Dexmedetomidine, α2-2 adrenergic receptor agonist, adjuvant, analgesic
D
exmedetomidine is a stereoisomer of
CH
medetomidine, with chemical formula 4-[(1S)- CH
H
1-(2, 3-dimethylphenyl) ethyl]-1H-imidazole. N CH
It is a highly selective α2-adrenergic receptor (AR) O H
agonist with a relatively high ratio of α2/ α1-activity
N
(1620:1 as compared to 220:1 for clonidine).1 H
Indian Journal of Clinical Practice, Vol. 24, No. 3, August 2013 223
ANESTHESIOLOGY
an adjuvant to local anesthetics. They prolong the the safety profile of dexmedetomidine, it is now being
duration of analgesia by blocking the so-called used intrathecally without apparent toxicity.4,6
hyperpolarization-activated cation current (Ih current).
Other useful effects of activation of α2-ARs include
This is the most well-defined mechanism of α2-AR
decreased salivation, increased glomerular filtration,
agonists. After an action potential (AP) has occurred,
decreased intraocular pressure and increased seizure
the nerve will have to repolarize to be able to produce
threshold.1
new APs. The early repolarization phase will result in
a hyperpolarized state that will make the generation of Adjuvant
new APs virtually impossible, and the nerve is, during
this period, judged to be refractory to stimulation. Dexmedetomidine exhibits synergism with local
Thus, blocking the Ih current will result in prolonged anesthetics, prolonging their duration of action. So far,
hyperpolarization of the nerve, which in turn will result the clinical evidence for the use of dexmedetomidine
in an analgesic action. Blocking the Ih current may also as an adjuvant to local anesthetic for peripheral nerve
have the potential to produce a selective sensory effect blocks is limited to few animal studies and three human
as this effect appears to be more pronounced in C fibers studies.3,4,6-8
(pain) than in A alpha fibers (motor). Dexmedetomidine
has more pronounced effect on inhibition of nerve fiber In the spinal cord, activation of both a-2C and a2-
action potentials as compared to clonidine.5 ARs, situated in the neurons of superficial dorsal horn
especially lamina II, directly reduces pain transmission
Centrally, α2-AR agonists cause analgesia and sedation
by reducing the release of pronociceptive transmitter,
by inhibition of substance P release in the nociceptive
pathway at the level of the dorsal root neuron and by substance P and glutamate from primary afferent
activation of α2-AR in the locus coeruleus. Suppression terminals and by hyperpolarizing spinal interneurons
of activity in the descending noradrenergic pathway, via G-protein-mediated activation of potassium
which modulates nociceptive neurotransmission, channels. Postsynaptic activation of central a2-ARs
terminates propagation of pain signals leading to results in sympatholytic effect leading to hypotension
analgesia.1 and bradycardia, an effect judiciously used to attenuate
Apart from above mechanisms, clonidine may reduce the stress response of surgery.9-13
systemic uptake of the perineurally deposited local The greater a2-ARs selectivity of dexmedetomidine
anesthetic-clonidine mixture by means of a1-receptor- enhances the therapeutic window of dexmedetomidine
mediated vasoconstriction. As dexmedetomidine has a in the treatment of pain. Its opiate sparing effect has
very limited effect on a1-ARs, it is unlikely that a nerve important implications for the management of acute
block by a local anesthetic-dexmedetomidine mixture postoperative pain and chronic pain states, including
may prolong the block duration by this mechanism, disorders involving spasticity or myofascial pain,
despite being able to cause time limited vasoconstriction
neuropathic pain, sympathetically maintained pain
by stimulation of α2-ARs.5
such as complex regional pain syndrome (CRPS) and
The upcoming anti-inflammatory effects of α2-AR chronic daily headaches. It is evolving as an adjuvant
agonists has been highlighted by a series of animal analgesic, both as intravenous and intrathecal infusion,
studies by Brummett and colleagues who reported that in cancer pain refractory to multiple treatment
large doses of dexmedetomidine or clonidine prolonged modalities.14-16
the duration of sciatic nerve block when added to local
anesthetics like bupivacaine or ropivacaine in rats. Conclusion
In addition, histopathological examinations of sciatic
nerves at 24 hours and 14 days showed that the nerve Dexmedetomidine has evolved as a panacea for various
axon and myelin were unaffected after perineural applications/procedures with multiple promising
application of dexmedetomidine. There was decrease delivery routes. Its clinical applications in adults and
in proinflammatory products from immune cells children include premedication, as part of multimodal
recruited to the site of injury and an increase in anti- anesthetic regimen, regional anesthesia, sedation
inflammatory cytokines. Hence, there was decrease monitored anesthesia care, procedural sedation,
in perineural inflammation as compared to sole prevention/treatment of emergence delirium, alcohol
use of local anesthetic. These findings reinforce the withdrawal and shivering, and the list continues to
neuroprotective role of dexmedetomidine. Because of grow.
224 Indian Journal of Clinical Practice, Vol. 24, No. 3, August 2013
ANESTHESIOLOGY
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