dexmedetomidina neuroanestesia

C

Anesthesia for functional neuro
surgery:
the role of dexmedetomidineIrene Rozet

Department of Anesthesiology, Harborview MedicalCenter, Seattle, Washington, USA

Correspondence to Irene Rozet, MD, Department ofAnesthesiology, Harborview Medical Center, 325 NinthAvenue, Box 359724, Seattle, WA 98104, USATel: +1 206 744 3059; fax: +1 206 744 8090;e-mail: [email protected]

Current Opinion in Anaesthesiology 2008,21:537–543

Purpose of review

The purpose of this review is to summarize current approaches to the anesthetic

management of functional neurosurgery and to describe the application of an

a-2-adrenergic agonist dexmedetomidine in the anesthetic management of functional

neurosurgical procedures.

Recent findings

Dexmedetomidine, an a-2-adrenergic agonist, causes a unique kind of sedation, acting

on the subcortical areas, which resembles natural sleep without respiratory depression.

Experimental data demonstrate both cerebral vasoconstriction and vasodilatation,

depending on the model and dose studied. At the clinically relevant doses,

dexmedetomidine decreases cerebral blood flow and cerebral metabolic rate of oxygen

in healthy volunteers. Clinical experience of dexmedetomidine use in functional

neurosurgery is limited to small case-series. Nevertheless, these reports indicate that

use of dexmedetomidine does not interfere with electrophysiologic monitoring, thus

allowing brain mapping during awake craniotomy and microelectrode recording during

implantation of deep-brain stimulators.

Summary

Dexmedetomidine has been demonstrated to provide a successful sedation without

impairment of electrophysiologic monitoring in functional neurosurgery. Prospective

randomized studies are warranted to delineate an optimal regimen of dexmedetomidine

sedation and any dose-related influence on neurophysiologic function.

Keywords

awake craniotomy, dexmedetomidine, implantation of deep brain stimulator

Curr Opin Anaesthesiol 21:537–543� 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins0952-7907

Introduction‘Functional neurosurgery’ is a broad term applied to a

variety of neurosurgical procedures in which monitoring

of brain function during the procedure is crucial for

localization of the area of surgical interest and successful

outcome. Anesthetic management for these procedures is

challenging because intraoperative monitoring requires

fully preserved brain function. This is a direct contra-

diction of the essential goal of anesthesiology, which is

to provide the patient with sedation, analgesia, and

anesthesia.

Dexmedetomidine, an a-2-adrenergic agonist, acting at

the subcortical areas of the brain and not involving the

g-amino-butyric acid (GABA) receptors, provides a seda-

tion, which resembles natural sleep, without respiratory

depression. These unique properties of dexmedetomi-

dine make it a potentially advantageous sedative agent

for functional neurosurgery.

opyright © Lippincott Williams & Wilkins. Unauth

0952-7907 � 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins

The review discusses the challenges and current

approaches of anesthetic management, including clinical

applications of dexmedetomidine, for the two most pop-

ular functional neurosurgical procedures requiring an

awake cooperative patient and fully preserved cerebral

electrophysiology: ‘awake’ craniotomy requiring brain

mapping, and implantation of deep brain stimulators

for movement disorders.

General principles of anesthetic managementof functional neurosurgeryIdeal perioperative management for functional neurosur-

gery should satisfy multiple anesthetic and surgical goals

simultaneously. These objectives include patient com-

fort and analgesia, patient immobility throughout the

procedure (often for a long duration), adequate oxygen-

ation and ventilation, hemodynamic stability, optimal

brain conditions, prevention of brain swelling, and full

orized reproduction of this article is prohibited.

DOI:10.1097/ACO.0b013e32830edafd

mailto:[email protected]

http://dx.doi.org/10.1097/ACO.0b013e32830edafd

C

538 Neuroanaesthesia

patient cooperation with intact electrophysiologic moni-

toring. Obviously, the above-mentioned conditions often

contradict each other, making ‘anesthetic’ management

for awake neurosurgical procedures one of the most

challenging in anesthesia practice.

The kind of neurologic monitoring required for func-

tional neurosurgery depends on the procedure and the

area of interest in the brain. An assessment of cognitive

function, speech, vision, and motor function is required in

surgery for resection of brain tumors or epileptic focus

located close to the eloquent cortex (Broca’s and

Wernicke’s speech areas in the dominant frontal and

temporal lobe, motor strip, and visual cortex). During

implantation of a deep brain stimulator (DBS) for a patient

with movement disorder, an assessment of changes in

tremor or spasticity/rigidity in a fully awake patient is

mandatory. Intraoperative electrophysiologic testing for

tumor and epilepsy surgery includes electroencephalo-

graphy (EEG) and electrocorticography (ECocG) for

cortical brain mapping. The microelectrode recording

(MER) of impulses of subcortical areas, including sub-

thalamic nucleus, is used during DBS implantation.

Patient positioning for functional neurosurgery makes

access to the patient’s airway difficult, further complicat-

ing anesthesia management (Fig. 1).

Intraoperative ‘anesthetic’ management of awake craniot-

omy has changed during the last two decades. Anesthesia

medications with rapid onset of action and short half-lives

such as propofol and remifentanil replaced previously used

opyright © Lippincott Williams & Wilkins. Unautho

Figure 1 Positioning of patient for functional neurosurgery

Positio

Head fixation

PinsMayfield

frame

Head positionNeutralFlexion

ExtensionLateral flexion

PinsStereotactic

frame

Hoarshoegelpad

OR Tab

90˚

OR, operating room.

neuroleptanalgesia with fentanyl and droperidol. Multiple

anesthestic techniques are used for awake craniotomies:

monitored anesthesia care, conscious sedation, the

‘asleep–awake’ and ‘asleep–awake–asleep’ techniques

[1�]. The ‘asleep–awake–asleep’ technique is currently

considered as the most popular one [1�]. The first ‘asleep’

stage is provided with heavy sedation or even general

anesthesia in the beginning of the surgery during a

patient’s positioning, fixation of the head with pins, cra-

niotomy or burr holes, and final exposure of the brain. Skin

infiltration with local anesthetic at pin insertion sites and

the skin incision, or performance of a scalp nerve block,

are essential for pain relief and reducing opiates-related

complications [2]. A variety of different medications

and combinations of medications has been reported to

be successfully used: propofol, remifentanil, fentanyl,

midzolam [1�,3,4]. For airway management, oral or naso-

pharyngeal airways, oral and nasal endotracheal tubes,

laryngeal mask (LMA) as well as unprotected airway have

all been used with different degrees of success [1�]. For the

next awake stage, the patient must be brought to full

consciousness. In this awake phase, mapping of the brain

with electrocorticography during cognitive testing is per-

formed to delineate the area to be resected. The transition

from the ‘asleep’ to the ‘awake’ phase is the most challen-

ging task in the anesthetic management because of poten-

tial complications during the awakening and manipulation

of the airway, while the brain is exposed. Coughing,

Valsalva maneuver, vomiting and movement during extu-

bation of the airway may lead to disastrous complications

such as bleeding, brain swelling, venous air embolism, and

potentially death. Consequently, many anesthesiologists

rized reproduction of this article is prohibited.

ning

Supine SittingLateral

Body positioning

le

180˚

C

Anesthesia for functional neurosurgery Rozet 539

try to avoid airway instrumentation. When mapping is

completed, either sedation or analgesia or both may be

provided again for the ‘asleep’ phase. Airway instrumenta-

tion when the patient’s head is in pins and covered by the

surgical drapes may be difficult, especially if emergency

intubation of the trachea is required.

In implantations of DBS, the first ‘asleep’ phase usually

requires less time than the first ‘asleep’ phase in awake

craniotomy. DBS implantation does not require wide

exposure of the brain. Only burr holes are needed, which

can be performed under local infiltration of the scalp.

Although the use of various sedative techniques, includ-

ing propofol infusion, fentanyl, remifentanil, and inhala-

tional anesthetics have been reported [5,6�], many

surgeons prefer to avoid any sedation because of the

extreme sensitivity of subcortical areas to the GABA-

ergic medications, which may completely abolish MER

recording and tremor. When localization of the DBS

electrode is finalized, the patient’s head is disengaged

from the frame, and the patient may then be anesthe-

tized for the implantation of the generator into the

chest wall.


Table 1 Potential risks and complications expected in awake

functional neurosurgery

Undersedation Oversedation

General GeneralPain DrowsinessDiscomfort RestlessnessRestlessness Impaired cognition, lack of

cooperation, inability toperform mapping

AnxietyInability to stay still RespiratoryVoluntary movements Airway obstruction

Respiratory depressionHypoventilation

Respiratory HypercarbiaInability to clear secretions (PD) Oxygen desaturationCoughing ApneaDyspnea–hyperventilation Need for airway manipulations

and for providing anemergency airwayCoughing and Valsalva duringtransition from ‘asleep’ to‘awake’ stage

NeurologicalSeizures NeurologicalBrain swelling Brain swellingBleeding Seizures

BleedingHemodynamic

Arterial hypertension HemodynamicTachycardia, arrhythmia Arterial hypotension

Gastrointestinal GastrointestinalNausea, vomiting Nausea, vomiting

Aspiration of gastric contentsInvoluntary movementsShiveringSedative-induced dyskinesiasArterial hypotension

PD, Parkinson’s disease.

Potential risks involved in anesthetic management

for awake neurosurgical procedures are summarized in

Table 1. Unfortunately, the actual incidence of compli-

cations and therefore the optimal anesthetic management

are largely unknown due to the lack of prospective

randomized studies. Currently available data are incon-

clusive because the studies differ in: anesthetic manage-

ment, criteria applied for definitions of complications,

and study design. The largest retrospective chart review

of awake craniotomy by Skucas and Artru [3] reported

that airway problems occurred in 2% out of 332 cases of

asleep–awake–asleep technique using only propofol

infusion in patients with unsecured airway undergoing

epilepsy surgery. Manninen et al. [4] prospectively

randomized 50 patients undergoing tumor surgery with

brain mapping to receive sedation with propofol and

remifentanil infusion, or propofol and fentanyl, and

observed an incidence of respiratory complications as

high as 18% in this cohort, without any difference

between the two groups. Respiratory complications were

defined as any of following: a decrease in respiratory

rate, oxygen desaturation, or airway obstruction. Because

the majority of surgeons request the avoidance of any

sedation, the most significant challenge in DBS implan-

tations is the maintainance of hemodynamic stability and

the prevention/treatment of intraoperative hypertension,

a known risk factor for developing intracerebral hemor-

rhage. In the prospective study involving 128 patients

receiving DBS implantations for Parkinson’s disease with

intermittent infusion of propofol, about 60% of patients

developed intraoperative hypertension [7]. Intracerebral

hemorrhage is considered to be the most severe compli-

cation, with an incidence of 3.3–6% reported in the

prospective studies [8–10]. The incidence of respiratory

complications in DBS implantations is unknown.

Benzodiazepines, barbiturates, and opioids may deliver

patient comfort and hemodynamic stability, but they

may also depress electyrophysiologic activity of the brain,

interfere with mapping, and cause respiratory depression

and airway compromise. To achieve a balance between

uneventful awakening and avoidance of respiratory com-

plications, the pharmacokinetic-guided titration of propo-

fol andremifentanil using thetarget control infusion device

has been advocated in patients with Parkinson’s disease

[11] and for awake craniotomies [12]. These devices are not

yet approved for use in the United States.

In addition to obesity [3] and age [6�], which were

suggested by the retrospective chart reviews as risk factors,

other patient-related risk factors are less clear. Previously,

obstructive sleep apnea was considered as a potential risk

factor for perioperative respiratory complications [1�].

However, there are no data to support this. There is also

a paucity of data to predict who would be an ideal candi-

date for awake functional neurosurgery. According to the


C


current data, in most instances, only the lack of patient

cooperation will preclude awake neurosurgery. However,

factors including abnormal anatomy of the airway, pre-

sence of gastroesophageal reflux and obesity should be

considered as potential risk factors.

Dexmedetomidine: a unique sedative agentDexmedetomidine is a selective agonist of a2-adrenergic

receptors (a2-ARs) with high affinity to a2-ARs (a2:a1

effect ratio of 1620:1), which is eight times higher than with

clonidine. Dexmedetomidine has a rapid onset of action. It

undergoes biotransformation in the liver, and the kidneys

excrete about 95% of its metabolites. Its distribution half-

life is 6 min, and a clearance half-life is 2 h.

Presynaptic and postsynaptic a2-ARs are distributed over

vital organs (heart, pancreas, kidneys), blood vessels and

the central and the peripheral nervous system. Stimulation

of postsynaptic a2-ARs leads to hyperpolarization of

neuronal membrane, whereas stimulation of presynaptic

a2-ARs reduces the release of norepinephrine. In the

spinal cord, a2-ARs are predominantly postsynaptic, and

located in the dorsal horn. Activation of spinal a2-ARs

inhibits nociception, which most likely explains the

analgetic properties of dexmedetomidine. Both presyn-

aptic and postsynaptic a2-ARs are widely distributed in

the brain, particularly in the pons and medulla. The major

site of noradrenergic innervation in the brain with the

highest concentration of presynaptic a2-ARs is the locus

ceruleus, which is responsible for arousal, sleep, anxiety,

and withdrawal symptoms from drug addiction. As a result,

the central effect of dexmedetomidine, which is mani-

fested by anxiolysis and sedation, is noncortical and sub-

cortical in origin. It does not involve the GABA system and

consequently does not cause cognitive impairment or

disinhibition, differentiating dexmedetomidine from all

GABA-mimetic sedatives and anesthetics.

The mechanisms of anesthetic-induced effects on uncon-

sciousness and amnesia are not clear. Recently, both

cortex [13] and thalamus [14] have been suggested to

be primarily responsible for the anesthetic-induced

unconsciousness. The unusual subcortical form of dex-

medetomidine-induced sedation is characterized by an

easy and quick arousal, resembling natural sleep.

The neuroprotective properties of dexmedetomidine

have been demonstrated in various animal models of

cerebral ischemia [15–17]. There are recent experi-

mental data suggesting that in addition to a2-ARs, the

neuroprotective effect of dexmedetomidine may include

other pathways in the brain, independent of a2-ARs,

and most probably involve I1-imidazoline receptors in

the brainstem and hippocampus [18]. Further in-vivo

studies are required to support this suggestion and to


elucidate mechanisms of dexmedetomidine-induced

neuroprotection.

Postsynaptic a2-ARs are widely presented in smooth

muscles of conductance and resistance vessels. Both vaso-

dilatating [19–21] and vasoconstricting [21–24] effects of

dexmedetomidine on cerebral and spinal arteries and

venules have been reported in animal studies. These

contradictory results may be explained by the differences

between models, animal species, and the dose of dexme-

detomidine, as well as experimental conditions and back-

ground anesthesia, all of which can potentially modify

vascular reactivity to the drug. Current data suggest that

dexmedetomidine-induced cerebral vasoconstriction has a

direct nonendothelium-dependent mechanism, whereas

dexmedetomidine-induced vasodilatation may be endo-

thelium dependent and involve nitric oxide pathways.

However, the exact mechanisms of dexmedetomidine’s

effect on the cerebral vasculature have not been comple-

tely elucidated yet.

Regardless of the mechanisms involved, current human

studies on healthy volunteers clearly demonstrate that

dexmedetomidine decreases cerebral blood flow (CBF)

[25,26��]. Using a PET-scan in awake healthy volunteers,

Prielipp et al. [25] demonstrated a decrease in global CBF

by about 30% with intravenous infusion of dexmedetomi-

dine of only 0.2 mg/kg/hour for 30 min. Prielipp et al. [25]

suggested cerebral vasoconstriction as an underlying

mechanism of decreased CBF, which is in agreement with

the previous in-vitro data and one in-vivo study in dogs

[27]; however, a recent study by Drummond et al. [26��]

demonstrated a simultaneous decrease of CBF and

CMRO2 with dexmedetomidine in healthy volunteers.

In this study [26��] CBF was estimated by measuring

blood flow velocity in the middle cerebral arteries (Vmca)

using Transcranial Doppler Ultrasonography (TCD) and

CMRO2 was calculated by measuring oxygen saturation in

the jugular bulb. In healthy volunteers, dexmedetomidine

also preserves cerebral autoregulation but slightly

decreases carbon dioxide reactivity (A.M. Lam, personal

communication).

Although both anticonvulsant and proconvulsant effects

of dexmedetomidine have been shown in animal studies

[28–31], there are no data supporting proconvulsant

effects of dexmedetomidine in humans; however, a-2

agonists may produce epileptiform activity in some

patients with epilepsy. The underlying mechanism of

this phenomenon was suggested to resemble the epilepti-

form activity during sleep deprivation, as a-2 agonists

modulate pathways of natural sleep [32].

The effect of dexmedetomidine on ventilation is minimal.

Initially, administration of dexmedetomidine increases

arterial carbon dioxide (PaCO2), but it also leads to


C


an increase in respiratory rate, a process described as

‘hypercapnic arousal phenomenon’. Hypercapnic arousal

phenomenon is a specific respiratory response to dexme-

detomidine and is associated with partial awakening and

hyperventilation in response to an increase in PaCO2,

without significant respiratory depression even at the deep

level of sedation [33]. This phenomenon makes dexme-

detomidine a unique sedative agent lacking respiratory

depressive properties of central origin, and, in contrast, it

causes a natural sleep-like sedation without respiratory

depression and with an easy arousal.

Bradycardia and decrease in blood pressure (BP) are the

most common hemodynamic effects of dexmedetomi-

dine. However, a biphasic effect on BP, contingent on the

dose and the rate of infusion, may also be observed, with a

decrease in BP at low doses but an increase in BP at high

doses.

Clinical application of dexmedetomidine tofunctional neurosurgeryThe first successful use of dexmedetomidine in functional

neurosurgery was published in 2001 by Bekker et al. [34],

who reported sedation with dexmedetomidine in a patient

requiring language mapping for tumor resection. It was

followed by the discouraging report of the inability to

perform neurocognitive testing with dexmedetomidine

by Bustillo et al. [35]. This most probably occurred because

of concomitant use of fentanyl and midazolam. A number

of recent case series clearly demonstrate that dexmedeto-

midine may be successfully used in functional neurosur-

gery [6�,36,37�,38,39��].

Souter et al. [37�] were the first to report the use of

dexmedetomidine not just for sedation at the first ‘asleep’

phase in awake craniotomy but during language mapping

and electrocorticography (ECoG) recording. It was suc-

cessfully used in six patients with seizure disorders, with

three of them receiving dexmedetomidine only. All three

patients received continuous infusion of dexmedetomi-

dine at 0.3–0.7 mg/kg/hour, which was titrated to main-

tain sedation, guided by modified OAA/S score. One

patient developed a subclinical seizure detected by

EEG while being sedated with dexmedetomidine, thus

allowing the investigators to conclude that dexmedeto-

midine does not supress epileptiform activity and can be

used in patients with seizure disorders requiring brain

mapping [37�]. To prove this, Talke et al. [39��] prospec-

tively observed EEGs in five patients with intractable

seizures who received 0.5 mg/kg/hour of dexmedetomi-

dine, followed by a bolus of 0.5 mg/kg, and found that

there was no decrease in epileptiform activity. Moreover,

in some foci an increase in epileptiform activity was

observed. Oda et al. [40��] evaluated the influence of

dexmedetomidine on the ECoG recording in 11 patients


with temporal lobe epilepsy, anesthetized with 2.5% of

sevoflurane and hyperventilated to PaCO2 of 30 mmHg,

and demonstrated that the median frequency of ECoG

recording did not change at a plasma level of dexmede-

tomidine of 0.5 ng/ml, but decreased at 1.5 ng/ml. How-

ever, there was no change in spike activity. It is possible

that concomitant use of sevoflurane and hyperventilation

could potentially affect anticonvulsant or proconvulsant

activity of dexmedetomidine. To verify the dose-depen-

dent anticonvulsant versus proconvulsant effect of dex-

medetomidine, and its effect on the seizure activity when

other anesthetics are used concomitantly, prospective

randomized trials are required.

As mentioned above, most neurosurgeons are reluctant to

use any kind of sedation for DBS implantations when

MERs are utilized for the positioning of the DBS electrode

because of the profound suppressive effect of GABA-ergic

medications on the basal ganglia. At first, dexmedetomi-

dine had been reported to provide adequate sedation

without impairment of MER recordings in a series of 11

patients undergoing DBS implantations for Parkinson’s

disease [38], when dexmedetomidine was titrated to main-

tain sedation and guided by the modified OAA/S score.

When this cohort of patients was compared with the

historical control cases, dexmedetomidine provided better

hemodynamic stability and patient satisfaction [38].

Recently, Elias et al. [41��] demonstrated the depression

of MER recording with moderate/heavy sedation with

dexmedetomidine, defined as sleepy and unarousable

state, with a bispectral index less than 80. On the contrary,

in lightly sedated patients with a bispectral index higher

than 80, no depression of MER recording has been

observed. This was associated with the dexmedetomidine

infusion of 0.1–0.4 mg/kg/hour [41��]. Although dexmede-

tomidine has theoretical advantages over GABA-ergic

medications such as lack of respiratory depression, hemo-

dynamic stability, and possible ability to suppress GABA-

ergic drugs-induced dyskinesias [42], the optimal sedative

dose of dexmedetomidine, the incidence of complications

as well as benefits of dexmedetomidine use in DBS

implantations remain unknown and should be investigated

prospectively.

ConclusionCurrent data on the anesthetic techniques for functional

neurosurgery is provided by the retrospective chart

reviews and small prospective case series. With conven-

tional sedation for the awake craniotomy and implanation

of DBS, the patient is potentially at risk for respiratory

depression, discomfort and arterial hypertension.

Dexmedetomidine is a unique sedative agent, which

does not cause respiratory depression. It has been shown

to be safe in both awake craniotomy and DBS implan-


C


tations in small retrospective case series. The optimal

dose regimen of dexmedetomidine for functional neuro-

surgery is unknown.

Prospective randomized trials are necessary to elucidate:

an optimal anesthetic technique for awake craniotomy

and DBS implantation; incidence of complications,

including respiratory complications and hemodynamic

stability; safety and usefulness of combinations of differ-

ent anesthetics; dose–response of dexmedetomidine on

the electrocorticography and MER recording.

AcknowledgementThe author is grateful to Professor AM Lam for providing his data on theinfluence of dexmedetomidine on the cerebral autoregulation and carbondioxide reactivity in healthy volunteers, and to Professor CM Bernards forproviding his data and input on the influence of sedation and opioids onthe respiratory depression in patients with sleep apnea syndrome.

References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as:� of special interest�� of outstanding interest

Additional references related to this topic can also be found in the CurrentWorld Literature section in this issue (p. 684).

1

�Erickson KM, Cole DJ. Anesthetic considerations for awake craniotomy forepilepsy. Anesthesiol Clin 2007; 25:535–555.

This is the most recent meticulous review on the anesthetic techniques for awakecraniotomies.

2 Ayoub C, Girard F, Boudreault D, et al. A comparison between scalp nerveblock and morphine for transitional analgesia after remifentanil-basedanesthesia in neurosurgery. Anesth Analg 2006; 103:1237–1240.

3 Skucas AP, Artru AA. Anesthetic complications of awake craniotomies forepilepsy surgery. Anesth Analg 2006; 102:882–887.

4 Manninen PH, Balki M, Lukitto K, Bernstein M. Patient satisfaction with awakecraniotomy for tumor surgery: a comparison of remifentanil and fentanyl inconjunction with propofol. Anesth Analg 2006; 102:237–242.

5 Venkatraghavan L, Manninen P, Mak P, et al. Anesthesia for functional neuro-surgery: review of complications. J Neurosurg Anesthesiol 2006; 18:64–67.

6

�Khatib R, Ebrahim Z, Rezai A, et al. Perioperative events during deep brainstimulation: the experience at cleveland clinic. J Neurosurg Anesthesiol 2008;20:36–40.

Large retrospective chart review of complications of DBS implantations in250 patients, showing age as an independent risk factor.

7 Santos P, Valero R, Arguis MJ, et al. Preoperative adverse events duringstereotactic microelectrode-guided deep brain surgery in Parkinson’s dis-ease. Rev Esp Anestesiol Reanim 2004; 51:523–530.

8 Deep-Brain Stimulation for Parkinson’s Disease Study Group. Deep-brainstimulation of the subthalamic nucleus or the pars interna of the globuspallidus in Parkinson’s disease. N Engl J Med 2001; 345:956–963.

9 Tir M, Devos D, Blond S, et al. Exhaustive, one-year follow-up of subthalamicnucleus deep brain stimulation in a large, single-center cohort of parkinsonianpatients. Neurosurgery 2007; 61:297–304.

10 Binder DK, Rau GM, Starr PA. Risk factors for hemorrhage during micro-electrode-guided deep brain stimulator implantation for movement disorders.Neurosurgery 2005; 56:722–732.

11 Fabregas N, Rapado J, Gambus PL, et al. Modeling of the sedative and airwayobstruction effects of propofol in patients with Parkinson disease undergoingstereotactic surgery. Anesthesiology 2002; 97:1378–1386.

12 Lobo F, Beiras A. Propofol and remifentanil effect-site concentrations estimatedby pharmacokinetic simulation and bispectral index monitoring during craniot-omy with intraoperative awakening for brain tumor resection. J NeurosurgAnesthesiol 2007; 19:183–189.

13 Velly LJ, Rey MF, Bruder NJ, et al. Differential dynamic of action on cortical andsubcortical structures of anesthetic agents during induction of anesthesia.Anesthesiology 2007; 107:202–212.


14 Alkire MT, McReynolds JR, Hahn EL, Trivedi AN. Thalamic microinjectionof nicotine reverses sevoflurane-induced loss of righting reflex in the rat.Anesthesiology 2007; 107:264–272.

15 Hoffman WE, Kochs E, Werner C, et al. Dexmedetomidine improves neu-rologic outcome from incomplete ischemia in the rat. Reversal by the alpha2-adrenergic antagonist atipamezole. Anesthesiology 1991; 75:328–332.

16 Kuhmonen J, Pokorny J, Miettinen R, et al. Neuroprotective effects of dexme-detomidine in the gerbil hippocampus after transient global ischemia.Anesthesiology 1997; 87:371–377.

17 Kuhmonen J, Haapalinna A, Sivenius J. Effects of dexmedetomidine aftertransient and permanent occlusion of the middle cerebral artery in the rat.J Neural Transm 2001; 108:261–271.

18 Dahmani S, Paris A, Jannier V, et al. Dexmedetomidine increases hippocampalphosphorylated extracellular signal-regulated protein kinase 1 and 2 contentby an alpha 2-adrenoceptor-independent mechanism: evidence for theinvolvement of imidazoline I1 receptors. Anesthesiology 2008; 108:457–466.

19 Bryan RM Jr, Steenberg ML, Eichler MY, et al. Permissive role of NO in alpha2-adrenoceptor-mediated dilations in rat cerebral arteries. Am J Physiol 1995;269:1171–1174.

20 Bryan RM Jr, Eichler MY, Swafford MW, et al. Stimulation of alpha 2 adreno-ceptors dilates the rat middle cerebral artery. Anesthesiology 1996; 85:82–90.

21 Iida H, Ohata H, Iida M, et al. Direct effects of alpha1- and alpha2-adrenergicagonists on spinal and cerebral pial vessels in dogs. Anesthesiology 1999;91:479–485.

22 Ganjoo P, Farber NE, Hudetz A, et al. In vivo effects of dexmedetomidine onlaser-Doppler flow and pial arteriolar diameter. Anesthesiology 1998;88:429–439.

23 Ishiyama T, Dohi S, Iida H, et al. Mechanisms of dexmedetomidine-inducedcerebrovascular effects in canine in vivo experiments. Anesth Analg 1995;81:1208–1215.

24 Iida H, Iida M, Ohata H, et al. Hypothermia attenuates the vasodilator effects ofdexmedetomidine on pial vessels in rabbits in vivo. Anesth Analg 2004;98:477–482.

25 Prielipp RC, Wall MH, Tobin JR, et al. Dexmedetomidine-induced sedation involunteers decreases regional and global cerebral blood flow. Anesth Analg2002; 95:1052–1059.

26

��Drummond JC, Dao AV, Roth DM, et al. Effect of dexmedetomidine oncerebral blood flow velocity, cerebral metabolic rate, and carbon dioxideresponse in normal humans. Anesthesiology 2008; 108:225–232.

Healthy volunteers study demonstrated a concomitant decrease of cerebralmetabolic rate of oxygen and cerebral blood flow with dexmedetomidine.

27 Zornow MH, Fleischer JE, Scheller MS, et al. Dexmedetomidine, an alpha2-adrenergic agonist, decreases cerebral blood flow in the isoflurane-anesthetized dog. Anesth Analg 1990; 70:624–630.

28 Mirski MA, Rossell LA, McPherson RW, Traystman RJ. Dexmedetomidinedecreases seizure threshold in a rat model of experimental generalizedepilepsy. Anesthesiology 1994; 81:1422–1428.

29 Whittington RA, Virag L, Vulliemoz Y, et al. Dexmedetomidine increases thecocaine seizure threshold in rats. Anesthesiology 2002; 97:693–700.

30 Tanaka K, Oda Y, Funao T, et al. Dexmedetomidine decreases the convulsivepotency of bupivacaine and levobupivacaine in rats: involvement of alpha2-adrenoceptor for controlling convulsions. Anesth Analg 2005; 100:687–696.

31 Halonen T, Kotti T, Tuunanen J, et al. Alpha 2-adrenoceptor agonist, dexme-detomidine, protects against kainic acid-induced convulsions and neuronaldamage. Brain Res 1995; 693:217–224.

32 Nelson LE, Lu J, Guo T, et al. The alpha2-adrenoceptor agonist dexmede-tomidine converges on an endogenous sleep-promoting pathway to exert itssedative effects. Anesthesiology 2003; 98:428–436.

33 Hsu YW, Cortinez LI, Robertson KM, et al. Dexmedetomidine pharmacody-namics: part I: crossover comparison of the respiratory effects of dexmedeto-midine and remifentanil in healthy volunteers. Anesthesiology 2004; 101:1066–1076.

34 Bekker AY, Kaufman B, Samir H, Doyle W. The use of dexmedetomidineinfusion for awake craniotomy. Anesth Analg 2001; 92:1251–1253.

35 Bustillo MA, Lazar RM, Finck AD, et al. Dexmedetomidine may impair cognitivetesting during endovascular embolization of cerebral arteriovenous malforma-tions: a retrospective case report series. J Neurosurg Anesthesiol 2002;14:209–212.

36 Ard JL Jr, Bekker AY, Doyle WK. Dexmedetomidine in awake craniotomy: atechnical note. Surg Neurol 2005; 63:114–116.


C


37

�Souter MJ, Rozet I, Ojemann JG, et al. Dexmedetomidine sedation duringawake craniotomy for seizure resection: effects on electrocorticography.J Neurosurg Anesthesiol 2007; 19:38–44.

Dexmedetomidine was successfully used during brain mapping.

38 Rozet I, Muangman S, Vavilala MS, et al. Clinical experience with dexmede-tomidine for implantation of deep brain stimulators in Parkinson’s disease.Anesth Analg 2006; 103:1224–1228.

39

��Talke P, Stapelfeldt C, Garcia P. Dexmedetomidine does not reduce epilepti-form discharges in adults with epilepsy. J Neurosurg Anesthesiol 2007;19:195–199.

Prospective study in five patients, showing some proconvulsant effect of dexme-detomidine.


40

��Oda Y, Toriyama S, Tanaka K, et al. The effect of dexmedetomidine onelectrocorticography in patients with temporal lobe epilepsy under sevoflur-ane anesthesia. Anesth Analg 2007; 105:1272–1277.

Prospective study showing depressive effect of dexmedetomidine on ECoG undersevoflurane anesthesia.

41

��Elias WJ, Durieux ME, Huss D, Frysinger RC. Dexmedetomidine and arousalaffect subthalamic neurons. Mov Disord 2008.

Retospective study showing that the suppressing effect of dexmedetomidine on themicroelectrode recording in DBS implantations is associated with heavy sedation.

42 Deogaonkar A, Deogaonkar M, Lee JY, et al. Propofol-induced dyskinesiascontrolled with dexmedetomidine during deep brain stimulation surgery.Anesthesiology 2006; 104:1337–1339.


dexmedetomidina neuroanestesia

Education