Dexmedetomidine is a newer agent that may have applicability

in the INR setting. A potent, selective α2-agonist

with sedative, anxiolytic, and analgesic properties, it has now
received regulatory approval for sedation. Dexmedetomidine
is especially noteworthy for its ability to produce a state of
patient tranquility without depressing respiration. However,
there are two caveats to consider. Its effects on cerebral perfusion
are still unclear.9 More importantly, there is a tendency
for patients managed with dexmedetomidine to have relatively
low blood pressure in the postoperative recovery period

Dexmedetomidine has now gained favor owing to its

unique property of inducing sedation with minimal respiratory
effects.20 It offers both anxiolytic and analgesic qualities.
Whether it possesses anticonvulsant and brain-protective
properties in humans remains to be demonstrated. This agent
is given as a loading dose of 1 μg/kg over 10 to 15 minutes and
then infused at 0.2 to 0.6 μg/kg/hr for the remainder of the procedure.
Doses are higher in children. Dexmedetomidine can
be used as a sole sedative agent and in combination with other
agents such as fentanyl.21 We prefer to use a low-dose propofol
infusion (25 to 75 μg/kg/min) that can be titrated to the
desired sedation depth. Others have reported good experience
with remifentanil combined with dexmedetomidine. 22 Propofol
and dexmedetomidine are discontinued 15 to 20 minutes
before intraoperative stimulation of motor and speech
areas, to allow adequate time for the patient‘s emergence
from sedation. Experience with dexmedetomidine has demonstrated
that some patients require more intense effort to be
roused from dexmedetomidine sedation (a physical stimulus
such as sternal rub and calling of the patient’s name). However,
once roused and engaged, the patient remains able to
cooperate with cognitive testing. At least one institution has
reported difficulty with cognitive testing in patients receiving
dexmedetomidine during Wada testing. It is possible the
excessive sedation was due to the use of additional sedative
agents, such as benzodiazepines, in combination with dexmedetomidine.
Some practitioners continue dexmedetomidine
during testing, albeit at a lower dose. Dexmedetomidine is
known to have a significant synergistic effect, and the sedative
effect will be greater when this agent is used in combination
with other sedative agents.

Patients who cannot tolerate

the procedure may benefit from dexmedetomidine; it
has been reported to reduce the need for antihypertensives
and to provide patient comfort without interfering with
electrophysiologic recordings.160 Dexmedetomidine has also
been reported to be useful for control of propofol-induced
dyskinesias.1]

In general, intravenous anesthetics cause a decrease in CBF

and CMRo2. However, these anesthetics might not be vasoconstrictors
in a strict sense, because in vitro barbiturates,
for example, dilate isolated cerebral vessels. The decrease in
CBF induced by most intravenous anesthetics appears to be
the result of reduced cerebral metabolism secondary to cerebral
functional depression. Among the intravenous anesthetics,
ketamine may be unique because it produces an increase
in both CBF and CMRo2. Table 5-2 summarizes the effects of
intravenous anesthetics on CBF, CMR, and ICP.

α2-Adrenergic Agonists
α2-Adrenergic agonists appear to be potent cerebral vasoconstrictors.
170 In most animal studies, α2 agonists decreased CBF
with little if any influence on CMRo2.170 The cerebrovascular
effects may depend on background anesthesia. The decrease in
CBF caused by dexmedetomidine was observed in dogs anesthetized
with isoflurane170 but not during pentobarbital anesthesia.
171 α2-Adrenergic agonists, topically applied through a
cranial window, constricted pial arteries and veins. This effect
was blocked by pretreatment of yohimbine, an α2 antagonist.
172 The pretreatment with glibenclamide, a blocker of the
ATP-sensitive potassium channel, potentiated the vasoconstriction
of pial arteries, indicating that α2-agonist–induced
activation of ATP-sensitive potassium channels as a counterbalancing
vasodilatory effect.172 Neither inhibition of NO
synthase
nor a blockade of β-adrenoreceptor affects the cerebral
vasoconstriction induced by dexmedetomidine. 173
In humans, dexmedetomidine decreased Vmca in a dose-dependent
manner, with the maximum reduction being
approximately 25% at the hypnotic doses.174 Dexmedetomidine
was also reported to decrease both rCBF and global
CBF.175 As to the metabolic effect, contrary to the data derived
from the animal investigations, dexmedetomidine reduced
CMR equivalent (CMRe; this value is calculated by multiplying
Vmca by the difference between arterial and cerebral jugular
venous oxygen contents) in healthy volunteers in a dosedependent
manner.176 The decreases in the CBF/CMR ratio
that were anticipated from animal studies were not observed.
A PET study in humans demonstrated a significant negative
linear correlation between clonidine concentration and rCBF
in the thalamus, prefrontal, orbital, and parietal association
cortex, posterior cingulate cortex, and precuneus, suggesting
that the pattern of regional deactivation during the sedation
induced by clonidine is very close to the pattern of the physiologic
early stage of non–rapid eye movement (REM) sleep.177
Because the metabolic effects of clonidine were not examined
in this study, the CBF/CMR ratio is not known.
Dexmedetomidine in a small dose decreased both MABP and
ICP, and in higher doses it did not influence ICP, despite a significant
increase in MABP in halothane-anesthetized rabbits. 178
In healthy human volunteers, oral administration of clonidine
5 μg/kg decreased Vmca by approximately 20% with slight attenuation
of CO2 reactivity.179 In severely head-injured patients,
a single dose of clonidine (2.5 μg/kg IV) did not significantly
affect ICP but significantly reduced MABP and CPP.180
Some patients displayed a transient increase (>10 mm Hg)
in ICP concomitant with a decrease in MABP, which may
have resulted from a cerebral autoregulatory vasodilation
mechanism
In the past, sedation techniques have relied upon incremental
fentanyl (with or without droperidol) titrated against sedation
level and respiratory rate to provide conscious sedation. More
recently, infusions of propofol in conjunction with fentanyl
have been used with great success and target-controlled infusion
of propofol has been recommended. During epilepsy surgery,
patient-controlled sedation with propofol is associated with a
lower incidence of intraoperative seizures but a higher incidence
of transient respiratory depression. Most recently, remifentanil
has been used in conjunction with propofol to provide sedation
and analgesia during awake craniotomy. This is rapidly becoming
the technique of choice because it is safe and easy to use and has
a minimal risk of respiratory depression if carefully titrated and
monitored. Pharmacokinetic simulations have demonstrated
that changes in infusion rates of propofol and remifentanil are
quickly followed by changes in effect site concentrations, which
correspond well with the desired clinical changes in patient sedation
and analgesia.
a2-Adrenoreceptor agonists have potential application during
awake craniotomy because they provide analgesia and sedation
that is easily reversed with verbal stimulation; there is no risk
of respiratory depression. Dexmedetomidine (highly specific
a2-adrenoreceptor agonist) has been used as an adjunct during
awake epilepsy surgery to provide sedation and analgesia sufficient
to complete cortical mapping and tumour resection.
Airway management is generally uneventful during awake
craniotomy under sedation, although the use of a soft nasopharyngeal
airway to maintain airway patency has been described. However, sedation inevitably runs the risk
of apnoea and
airway obstruction and patient position is crucial; the lateral
position is least likely to result in airway obstruction. Equipment
for emergency airway control should be available
throughout awake craniotomy and options include endotracheal
intubation under direct vision, blind nasal intubation, fibreoptic
nasotracheal intubation and insertion of a laryngeal mask
airway (LMA).