Anesthesia for awake craniotomy: a how-to guide for the occasional practitioner
Can J Anesth/J Can Anesth
Anesthesia for awake craniotomy: a how-to guide for the occasional practitioner Anesthe´sie pour craniotomie e´veille´: guide pratique pour le praticien occasionnel
Lingzhong Meng 0 1 2 3
. David L. McDonagh 0 1 2 3
. Mitchel S. Berger 0 1 2 3
. Adrian W. Gelb 0 1 2 3
0 D. L. McDonagh, MD Departments of Anesthesiology & Pain Management, Neurological Surgery, Neurology & Neurotherapeutics, UT Southwestern Medical Center , Dallas, TX , USA
1 L. Meng, MD A. W. Gelb, MBChB Department of Anesthesia and Perioperative Care, University of California San Francisco , San Francisco, CA , USA
2 L. Meng, MD (&) Department of Anesthesiology, Yale University School of Medicine , 330 Cedar Street, TMP 3, New Haven, CT 06520 , USA
3 M. S. Berger, MD Department of Neurological Surgery, University of California San Francisco , San Francisco, CA , USA
Awake craniotomy (AC), defined as the performance of at least part of an open cranial procedure with the patient awake, has been tied to beneficial outcomes compared with similar surgery under general anesthesia. Improved anesthetic techniques have made a major contribution to the increasing popularity of AC. However, the heterogeneity of practice among institutions doing large numbers of ACs raises questions (often among those who only occasionally perform AC - i.e., practitioners in low-volume AC institutions) as to the ideal anesthetic technique for AC. The procedure presents a variety of decision-making dilemmas, the origins of which are the varying institutional preferences, lack of quality evidence, and several practice controversies. Evidence-based data that support a single anesthetic algorithm for AC are sparse. In this narrative review, the technical nuances of 13 aspects of anesthetic care for AC are discussed based on institutional preferences and available evidence, and the various controversies and research priorities are discussed. The skills, experience, and commitment of both the surgeon and the anesthesiologist are large variables that are likely more important than what the literature suggests about ''best'' techniques for AC. Optimizing patient outcome is the fundamental goal of the anesthesiologist.
Re´sume´ La craniotomie e´veille´ (CE), de´finie comme la
re´alisation — au moins en partie — d’une proce´dure
craˆ nienne ouverte alors que le patient est e´veille´, a e´te´
associe´e a` des re´sultats favorables, comparativement a` la
meˆme intervention pratique´e sous anesthe´sie ge´ne´rale.
L’ame´lioration des techniques anesthe´siques a largement
contribue´ a` rendre la CE plus populaire. Cependant,
l’he´te´roge´ne´ite´ des pratiques entre les e´tablissements
pratiquant de grands nombres de CE soule`ve des
questions (souvent parmi ceux qui n’en font que
rarement, c’est-a`-dire, les praticiens exerc¸ant dans des
e´tablissements a` faibles volumes de CE) autour de la
technique anesthe´sique ide´ale pour cette intervention. La
proce´dure pre´sente un certain nombre de prises de
de´cision de´licates dont les origines tiennent aux
pre´fe´rences des diffe´rents e´tablissements, au manque de
qualite´ des donne´es probantes et a` plusieurs controverses
sur la pratique. Les donne´es probantes reposant sur des
preuves et en faveur d’un algorithme anesthe´sique unique
pour la CE sont rares. Dans cette e´tude narrative, les
nuances techniques de 13 aspects des soins anesthe´siques
pour CE sont discute´es en fonction des pre´fe´rences des
e´tablissements et des donne´es probantes disponibles; les
diffe´rentes controverses et les priorite´s en matie`re de
recherche sont e´galement discute´es. Les compe´tences,
l’expe´rience et l’engagement du chirurgien et de
l’anesthe´siologiste sont de grandes variables qui sont
susceptibles d’eˆtre plus importantes que ne le sugge`re la
litte´rature sur les « meilleures » techniques pour la CE.
L’optimisation des re´sultats pour les patients est l’objectif
fondamental de l’anesthe´siologiste.
Awake craniotomy (AC) is the performance of at least part
of an open intracranial procedure with the patient awake.
The first AC was performed in London, UK, on May 25,
1886 when Sir Victor Horsley, then a 29-yr-old surgeon,
resected an epileptogenic lesion from a 22-yr-old man.1
Subsequently, other pioneers, led by Wilder Penfield in
Canada, popularized the concept of AC through the first
half of the 20th century.2,3 During the late 1980s, AC
became an important treatment approach – and the standard
of care in the eyes of some experts4-6 – for brain tumours
(primarily gliomas) that are in close proximity to or reside
within the eloquent brain (i.e., sensorimotor or language
Accumulating evidence suggests that, compared with
surgery under general anesthesia (GA), AC is associated
with improved outcomes, including greater extent of
tumour resection,8,10 fewer late neurological deficits,8,10
shorter hospital stay,6,11 and longer survival,8 especially
after brain tumour resection. The improvements in
anesthetic care have made a major contribution to the
success of modern AC, and a variety of anesthetic
techniques have been reported and summarized.6,12-43
For the anesthesiologist from an institution that
performs a small volume of AC cases, questions often
arise as to the ideal anesthetic technique for this procedure.
This same question is valid for an experienced
anesthesiologist from a high-volume AC centre. For
example, the comparative efficacy of GA using a
laryngeal mask airway (LMA) compared with monitored
anesthesia care (MAC), with the patient lightly to
moderately sedated during the pre-awake phase of AC, is
a subject that is frequently raised but not yet settled in an
evidence-based manner.44,45 Therefore, with the aim of
optimizing individual patient outcomes, we specifically
discuss the preferences, evidence, and controversies of the
various anesthetic aspects for AC to further improve the
quality of perioperative care for this unique neurosurgical
A total of 13 anesthetic aspects of AC were chosen for
this review. Our aim was to discuss the technical nuances
of each aspect based on both institutional preferences and
the available evidence. The various controversies and
research priorities of AC are also discussed.
Patient selection: the non-surgical contraindications
At present, there is little consensus on the non-surgical
contraindications for AC, with one physician’s indication
sometimes another’s contraindication. For example, there
are reports of AC being done in patients having serious
medical conditions, such as chronic heart failure (with an
estimated ejection fraction of 10%)46 or a third-trimester
twin pregnancy with the parturient in a looming
neurological crisis.47 The age of patients who have
undergone AC also varies widely. Indeed, one report
documented the perioperative course of a nine-year-old
boy – probably the youngest patient on record – who
underwent AC to resect a recurrent high-grade
glioblastoma.48 Programs at the University of California
San Francisco and Toronto Western Hospital have reported
age ranges of 13-83 yr (n = 611 patients)6 and 12-90 yr (n =
610 patients),7 respectively. Overall, patient refusal is
arguably the only absolute non-surgical contraindication to
AC. Other non-surgical factors – claustrophobia,
uncontrolled coughing, inability to remain still, extremely
young age, morbid obesity, cognitive disorders (e.g.,
dementia, Down’s syndrome), mood instability – should
be regarded as relative contraindications.
Importance of good patient rapport
The path to successful AC begins with the preoperative
patient interview. Compared with surgery under GA, the
preoperative interview is a particularly important step.
Gaining the patient’s trust aids in mitigating anxiety and
facilitates the constant face-to-face interactions between
the patient and caregivers that are needed during the awake
phase of surgery. Explanations of why and why not to
undergo AC enhances the patient’s engagement. Prior to
surgery, the perioperative team, including surgeon,
anesthesiologist, and nurse, should visit, introduce
themselves, answer questions, and establish a rapport
with the patient. Details including positioning, urinary
catheter placement, and noise related to craniectomy,
amongst other subjects, should be carefully explained. The
preoperative visit also allows an opportunity for patients to
rehearse the various mapping-related tasks with
neurophysiologists before surgery. Obtaining some
personal patient details that can serve as topics of
conversation (e.g., an interest in sports or travel) during
the awake phase can be useful. Reassurance and empathy
facilitate the establishment of good patient rapport. The
fact that the anesthesiologist is always within hearing range
and usually visible to the patient should be emphasized, as
well as the team’s familiarity with caring for patients
during the procedure.
Some institutions routinely administer anticonvulsants and
corticosteroids before surgery, whereas others, if the
indication for AC is epilepsy, for example, withhold
anticonvulsants to facilitate cortical mapping. Medications
(e.g., midazolam, fentanyl, atropine, scopolamine) that
have the potential to impair neurocognitive function or
contribute to emergence confusion/delirium during the
intraoperative wake-up should be avoided (Table 1).24,50-52
That said, some practitioners would consider giving small
doses of midazolam to highly anxious younger patients
who have good preoperative neurologic function.
Intraoperative care can be divided into three sequential
phases based on how the anesthesia is managed: pre-awake
phase, awake phase, post-awake phase. The following
discussion is laid out based on this sequence of events.
Standard patient monitors – electrocardiography, blood
pressure, pulse oximetry, capnography, temperature –
should be applied.53 Some institutions routinely place an
intra-arterial catheter to monitor blood pressure, whereas
others rely only on non-invasive blood pressure
measurements. Consideration should be given to placing
the blood pressure monitor on the arm that is ipsilateral to
the brain lesion so as not to interfere with the sensorimotor
monitoring of the arm that is contralateral to the brain
lesion. This should be done similarly with the pulse
oximetry probe – i.e., placing it on the finger or toe that is
ipsilateral to the brain lesion to prevent the oximetry cable
from limiting the range of motion of the arm that is
contralateral to the brain lesion. If it is on the contralateral
arm, the intra-arterial and intravenous catheters can be
secured with transparent dressings to allow detection of
any subtle motor responses that might otherwise be
obscured under dressings. These choices, however, are
clearly institutional preferences. End-tidal carbon dioxide
(EtCO2) should be monitored via the sampling channel
integrated into nasal cannula tubing (i.e., a specially
designed or modified conventional cannula) or connected
to the breathing circuit, depending on the method of airway
management. The respiratory rate but not the EtCO2 can
also be monitored using breathing cycle-induced
electrocardiogram variation integrated into many standard
monitoring platforms. Placement of an urinary catheter is
facilitated by intravenous sedation and intra-urethral
lidocaine application. Urethral lidocaine (e.g., URO-Jet ,
Amphastar Pharmaceuticals, Inc., Rancho Cucamonga,
CA, USA) is important for minimizing catheter-related
urinary irritation, which is a common cause of
Intraoperative language and sensorimotor mapping is
normally tasked to a trained neurophysiologist and
regarded as a surgical aspect of AC. The use of
intraoperative stimulation mapping is one of the core
components of AC and, based on a meta-analysis of
available data, has been associated with fewer late severe
Anticonvulsants (e.g., levetiracetam)
Steroids (e.g. dexamethasone)
5-HT3 receptor antagonist (e.g., ondansetron)
Neurokinin receptor antagonist (e.g., aprepitant)
Benzodiazepines (e.g., midazolam)
Opioids (e.g., fentanyl)
Anticholinergic (e.g., atropine or scopolamine)
NSAIDs (e.g., acetaminophen)
Antacids (e.g., famotidine)
Frequently administered to reduce the chance of perioperative seizure
Normally administered to reduce peri-tumor edema
May adversely affect neurocognitive function;49 consider only if there is
May cause nausea, itchy nose and dizziness; consider only if there is intractable pain
May cause dry mouth and emergence delirium; not recommended
Oral or iv acetaminophen can be a useful analgesic adjunct
May consider if gastroesophageal reflux disease
Possesses unwarranted neurologic effect, may cause dystonic reactions; not recommended
Previously used for neuroleptanalgesic anesthesia, may impede neurocognitive testing; not
May cause hypotension and long-lasting sedation; not recommended
*Based largely on authors’ institutional preferences. NSAIDs = non-steroidal anti-inflammatory drugs.
neurologic deficits and more extensive tumour resection.10
Some institutions use electrocorticography (i.e., brain
electrical activity recorded directly from the cortex) to
detect epileptiform activity and warn the surgeon of
stimulation-induced after-discharge activity (as an
indication of excessive stimulation current).6 Phase
reversal of somatosensory evoked potentials can be used
to identify the central sulcus during the pre-awake phase,
although it is not typically used in an awake patient.
Heterogeneity exists in the use of intraoperative
stimulation mapping and neurophysiological monitoring
techniques. The technical details of intraoperative mapping
can be found in other published reports.4-6
Patient positioning and the operating room bed
The operating room bed is typically turned 90 (in
reference to the anesthesia workstation) to either left or
right depending on the side of the brain lesion. This
maneuver positions the patient facing the anesthesia
workstation, which makes the face-to-face interaction
during the awake phase convenient and facilitates any
airway management, if needed.
The patient can be positioned supine – laterally on an
axillary roll or semi-laterally with the back of the patient
resting on a round longitudinal pillow. The semi-lateral
position is preferred by some institutions because it
enhances the patient’s positional endurance, facilitates
surgical access to the lesion side of the brain, and makes
direct face-to-face or face-to-screen interaction possible
(Fig. 1A-D). It also facilitates spontaneous ventilation by
enhancing chest compliance in a patient with an obese
abdomen. An axillary roll can be used in the lateral
position but is normally not needed for the semi-lateral
Most institutions secure the patient’s head in a pinned
head frame after infiltrating the pin sites with local
anesthetics. A small number of institutions simply
support the head on a horseshoe frame or its equivalent.
Using a pinned head frame prevents the head from moving,
but it makes manipulation of the head/neck position during
airway emergency difficult and has the potential risk of
lacerating the scalp. In contrast, the use of horseshoe
support facilitates head/neck re-positioning during airway
management, although the patient may unintentionally
move the head, causing safety and sterilization concerns. A
minor turn of the patient’s head (away from the lesion side)
is frequently applied for the semi-lateral patient to facilitate
surgical access. It is usually well tolerated by the patient. A
‘‘sniffing’’ position for the head and neck (mild head
extension and anterior translocation) aids in optimizing
airway patency prior to securing the head frame to the
operating room bed at the start of the procedure.
Airway management during the pre-awake phase
Various techniques of airway management during the
preawake phase of AC have been described. The GA–awake–
GA (a.k.a. asleep–awake–asleep, or AAA) technique with an
endotracheal tube (ETT) placed before and after the awake
phase was originally described in 1998.17 A small tube
exchanger may be left endotracheally after extubation to
facilitate reintubation. This technique is laborious and is
prone to complications with inexperienced practitioners. The
tube exchanger left in the trachea for reintubation can affect
intraoperative language testing. An alternative to the
traditional AAA technique using an ETT is to use an LMA
during the pre-awake phase, remove the LMA during the
awake phase, and finish the case without the LMA during the
post-awake phase. Even though the LMA offers some airway
control, it does not guarantee satisfactory controlled
ventilation. Ineffective ventilation due to a malpositioned
LMA-related air leak, which can occur in a semi-laterally
positioned patient when the head is slightly rotated, can
cause undesired hypercapnia. Some institutions use
unilateral or bilateral nasopharyngeal airways (nasal
trumpet) attached to the breathing circuit in patients who
are spontaneously breathing but deeply sedated.43 The
disadvantage to this approach, although feasible, is the
difficulty/inability to apply positive-pressure ventilation to
A distinctive approach to airway management during AC
is avoidance of an LMA or ETT altogether – proceeding with
the pre-awake phase of AC under light to moderate sedation.
In this case, a nasal cannula (taped to both cheeks), with an
EtCO2 sampling channel, is used for supplemental oxygen
and monitoring respiration. Although a nasopharyngeal or
oropharyngeal airway is normally not needed, it can be
placed when necessary, facilitated by propofol sedation and
lidocaine paste. A drawback of this approach is hypercapnia
due to airway obstruction or hypoventilation, especially
when higher doses of propofol and/or remifentanil are used.
If airway obstruction or hypoventilation develops, one can
either add dexmedetomidine to minimize the dose of
propofol or remifentanil, or stop sedative infusions
altogether to awaken the patient.
The superiority of any one technique for airway
management during the pre-awake phase of AC is
unknown because of the lack of comparative studies.
General anesthesia vs light to moderate sedation during
the pre-awake phase
We define the patient as being under GA when an LMA or
ETT is placed or when the patient is deeply sedated without
an LMA or ETT. Otherwise, the patient is regarded as
being under light to moderate sedation (MAC). The
Fig. 1 Semi-lateral position for
awake craniotomy (A) with the
surgeon’s view (B), the
anesthesiologist’s view (C), and
the operating room layout (D)
shown. The body side (i.e.,
ipsilateral side) of the
hemisphere with the lesion is
the side that is up and supported
by a round longitudinal bolster
from shoulder to buttock. The
upper leg is elevated with
padding. The hip and knee of
the lower leg can flex slightly
for comfort. The upper arm rests
on the chest and abdomen. The
lower arm rests on an arm board
with the angle between arm
board and operating
table adjusted to patient’s
comfort. The patient’s head can
be slightly rotated to facilitate
surgeon’s access without
causing patient discomfort. A
right-angled bar is attached to
the head of the table as a
mechanism to tent the surgical
drape upward and open the
space in front of patient’s face
via which the patient can see the
testing screen on the side, and
the caregivers can reach in to
help the patient
advantages of GA include better airway control (if using an
LMA or ETT) and a motionless patient. The potential
drawbacks include, but are not limited to, (
unpredictable asleep-to-awake transition, (
drowsiness, and (
) emergence confusion/delirium – with
the risk of inflicting self-injury or jeopardizing meaningful
awake testing. Potential disadvantages of light to moderate
sedation for the pre-awake phase include movement,
talkativeness, and anxiety. The transition to being fully
awake, however, is much faster, more predictable, and less
It has been argued that the avoidance of GA-related
physiological disturbances, mechanical ventilation, and
potential anti-tumour immunity suppression might
contribute to the beneficial outcomes associated with AC,
when compared with surgery under GA,54 although the
validity of this proposition remains highly speculative.
Nonetheless, an important distinction is needed here
(Fig. 2). For craniotomy under GA, the anesthetic is
applied throughout the procedure, whereas with
conventional AC using an LMA the patient is exposed to
GA only during the pre-awake phase. Therefore, the
duration of GA for AC is much shorter than that for surgery
performed completely under GA (i.e., *1-2 hr vs *4-5
hr). This is different from the scenario where the pre-awake
phase of AC is performed under light to moderate sedation,
and the patient is never exposed to GA. The impact of GA
vs light to moderate sedation on outcomes in this setting is
unknown. It appears that the major institutions that perform
Craniotomy under general anesthesia
Resec on phase
Fig. 2 Comparison between craniotomy under general anesthesia
(GA) and awake craniotomy. Both surgical approaches are arbitrarily
divided into three phases. For craniotomy under GA, the GA is
applied throughout all three phases. For awake craniotomy, the
anesthetic technique during the pre-awake phase varies: GA with
endotracheal tube (ETT) vs GA with laryngeal mask airway (LMA) vs
monitored anesthesia care (MAC). There is no or minimal sedation/
analgesia during the awake phase. Currently, MAC is the most
popular anesthetic technique used during the post-awake phase
AC are split on their preferences – some prefer a sedation
level that renders the patient drowsy but readily arousable
and others prefer GA with an LMA.
Local anesthesia for analgesia The mainstay of analgesia during AC is local anesthesia via either field infiltration or scalp nerve block (typically using
*40-60 mL of 0.25% bupivacaine mixed with 1%
lidocaine [50:50] and 1:100,000 epinephrine).6,55,56 Field
infiltration and scalp nerve block are distinct approaches.
Some institutions rely solely on field infiltration, whereas
others combine field infiltration (primary modality) with
scalp nerve blocks as adjuncts. The efficacy of field
infiltration for controlling surgical pain during craniotomy
has been verified by both clinical experience and previous
studies.57,58 Some studies, however, suggest that the
analgesic efficacy of scalp nerve block is similar to that
of field infiltration for AC (as well as for craniotomy under
GA).56,59 Therefore, it is likely that, in experienced hands,
field infiltration and scalp nerve block are alternative local
anesthetic techniques. With adequate local anesthesia,
intravenous opioid administration is rarely needed during
AC. Subsequent injection of additional local anesthetics
into the incision site (including the dura) and across the
scalp flap is usually effective in relieving new-onset pain
that occurs during the surgery. According to the results of
some laboratory and retrospective studies, other advantages
attributable to local anesthetics include a neutral
neurocognitive effect and potential tumour-suppressive
effects.60-66 There is currently no consensus on the
choice or dose of local anesthetics for AC. Exuberant
application of local anesthetics has the potential to cause
seizures and other toxicities,67 as well as hypertension in
the case of inadvertent intravascular epinephrine injection.
Agents for sedation and GA
It is enlightening to revisit the evolution of anesthetic
regimens for AC, especially the story of the rise and fall of
each drug. What Horsley used in his AC patients was a
combination of morphine and chloroform, with the
chloroform discontinued during the case to awaken the
patient. Indeed, he noted that ‘‘…I have been very deeply
impressed with the startling rapidity with which a patient
who has roused up in the middle of the operation….’’1 The
advent of local anesthetics and their application in
neurosurgical patients revolutionized the practice of AC
during the first half of the 20th century.3,9,29,55 The concept
of neuroleptanesthesia (i.e., a state produced by the
combined administration of a potent neuroleptic and
narcotic drugs),68 introduced by De Castro and
Mundeleer in 1959, opened an era of using a
standardized sedation protocol consisting of droperidol
and fentanyl for AC that continued for more than three
decades.12 In 1988, Archer et al. reported their experience
with droperidol and fentanyl neuroleptanesthesia in 354
consecutive awake cases and found no perioperative
morbidity or mortality that could be attributed to
anesthesia.14 In 1992, Silbergeld et al. reported their
usage of propofol for AC.15 Since then, drugs featuring
rapid onset and offset, titratability, and minimal lingering
neurocognitive effects have become the mainstay for
sedation during AC (predominantly propofol and
remifentanil).16,18-23,28,34,37,51,52 The Chinese experience
of using acupuncture as the mainstay of anesthesia/
analgesia supplemented by meperidine and haloperidol
(or droperidol) for AC, with the first case performed in
1965, is an intriguing approach to minimize the use of the
drugs and their various adverse effects.13 Entering the 21st
century, the introduction of dexmedetomidine in AC
reflects its unique advantages of causing minimal
respiratory depression while providing sedation and some
An ideal drug for AC should possess such attributes as fast
onset/offset, minimal lingering neurological effect after
termination, and no depressive cardiovascular or respiratory
effects. It should also benefit disease-specific outcomes,
similar to the advantageous oncological effect (i.e., lower
incidence of recurrence and metastasis and longer survival)
that has been suggested, albeit lacking convincing data, for
propofol anesthesia.69-80 Unfortunately, there is currently no
such magic bullet. Every modern anesthetic drug used for
AC is a double-edged sword. Different patients may have
differing sensitivities to the same drug. Moreover, the drug
effect is almost always dose dependent. It is advisable not to
put forward an invariable protocol but to advocate a flexible
approach based on the needs and response of the individual
A recent retrospective study correlated the use of
inhalational anesthesia, compared with intravenous
anesthesia, with worse survival in cancer patients,
although the study was not specifically done on brain
tumour patients.69 If a cause–effect relation between the
choice of anesthetic agents and cancer patient survival is
eventually proven in prospective randomized controlled
trials, the anesthetic regimens for awake brain tumour
surgery and any oncological surgery requiring anesthetic
care must be re-considered.
A frequently used sedative regimen for AC is low-dose
propofol (20-50 lg kg-1 min-1 and remifentanil
(0.010.06 lg kg-1 min-1) infusions titrated to make the patient
drowsy but arousable – and without airway obstruction.
Remifentanil, albeit a narcotic, is chosen because it is
easily titratable, acts as a potent sedative (i.e., maintaining
a calm patient), and causes fewer gastrointestinal side
effects than fentanyl.81 Some institutions use
dexmedetomidine (0.3-0.5 lg kg-1 hr-1) as an adjunct
when the patient cannot be satisfactorily sedated by
propofol and remifentanil infusion or when airway
obstruction or hypoventilation mandates reduction or
cessation of propofol or remifentanil. The satisfactory
application of dexmedetomidine as a sole sedative agent
for AC has also been reported.30,82 The sedation provided
by propofol, remifentanil, or dexmedetomidine does not
appear to interfere with electrocorticography during
AC.16,18,23,30 If an LMA is used, a combination of
intravenous infusions (propofol *50-100 lg-1.min-1 and
remifentanil *0.1-0.2 lg kg-1 min-1) and/or inhalational
agents (sevoflurane or desflurane \ 0.5 minimum alveolar
concentration along with remifentanil *0.1-0.2
lg kg-1 min-1) is frequently used to effect a rapid
transition from asleep to awake with clear headedness.
If a deep plane of sedation or GA is used during the
preawake stage, preparedness for awakening the patient
should be started as early as possible. The surgeon
normally gives a time estimate for awakening the patient.
All sedative or hypnotic agents are typically discontinued
at the moment the bone flap is removed unless some asleep
cortical mapping is desired. The goal is to awaken the
patient smoothly and rapidly without agitation, confusion,
or drowsiness. Some anesthesiologists keep the
remifentanil infusion going at a low rate (*0.01-0.05
lg kg-1 min-1) to facilitate a smooth transition and
provide some analgesia during the awake phase.
The goal during the awake phase is to have the patient
engaged, cooperative, pain-free, and comfortable. A swab
soaked with ice-cold water can be used to wet the patient’s
lips and mouth for comfort. Similarly, ice chips work well
to optimize patient comfort and offer a temporary
distraction as they chew or suck the chips. Patients
frequently need help to scratch the skin around the
nostrils and the inner canthus/corner of the eyes for
opioid-related itching. Most patients ask to move their hips/
legs/arms because of positional discomfort. It is important
to instruct the patient not to move the head and shoulders
when making positional adjustments. The room
temperature should be adjusted for the patient’s comfort.
An air blanket can be used as needed to provide either
warm or cool air. Empathy, hand-holding, and reassurance
offer great support to patients and should always be
provided during the awake phase. Ongoing encouragement,
coaching, and conversation are essential. Finally, keep in
mind that bilingual patients may need bilingual language
testing as language function for the primary language may
not entirely overlap the secondary language.83
Emergence agitation and delirium can ensue on
awakening, especially if the pre-awake phase is done
under GA or deep sedation, and can be dangerous to the
patient and extremely difficult to manage. At this time,
there is no consensus on effective management.
Nevertheless, the following strategies can be used. The
first step is to ‘‘re-induce’’ anesthesia with a propofol bolus
(30-50 mg) while avoiding apnea. Dexmedetomidine
boluses of *0.1-0.2 lg kg-1 can be given prior to the
second wake-up attempt. A physostigmine bolus (0.5-1.0
mg) can also be used to ablate emergence delirium,
although evidence to support its use is weak.84,85 A
remifentanil infusion can be continued at a low rate
(*0.01-0.05 lg kg-1 min-1) during the re-awakening to
help with behavioral control. Finally, droperidol or
haloperidol can be administered prior to the re-awakening
(with awareness of the potential QT-prolonging effects).
Unfortunately, most of these medications have the
potential to impact immediate neurocognitive function
adversely, so a risk-benefit assessment is always needed
when treating patients with emergence agitation/delirium.
Effective prevention for emergence agitation and delirium
is unproven. It is prudent to minimize sedation in high-risk
patients (e.g., those with baseline cognitive dysfunction) or
choose drugs characterized by rapid offset and minimal
Somnolence on emergence leaves the anesthesiologist
with many fewer management options. Intravenous
caffeine is an option but has undefined efficacy.86
Dexmedetomidine is the only relatively longer-acting
sedative typically used for AC – i.e., it cannot be ‘‘taken
away’’ or reversed if the patient is slow to emerge into the
awake phase. Elderly patients seem particularly sensitive,87
so great caution should be exercised with
dexmedetomidine in these cases. Similarly, midazolam
should be avoided in elderly patients, especially those with
impaired hepatic or kidney function. Residual opioid
effects can be reversed with naloxone (40-120 lg iv,
repeated as needed).
Managing intraoperative complications
Imminent potential complications during AC that require
life-saving intervention are seizures and airway
emergencies. The reported incidence of intraoperative
seizure (type unspecified) ranges from 3% to 16% based
on case series with more than 300 patients.6,7,14,88,89
Seizures frequently occur during cortical and subcortical
stimulation mapping. The first line of treatment is irrigation
of the cortex with ice-cold crystalloid solution applied by
the neurosurgeon (repeated as necessary).6 Fortunately,
most intraoperative seizures can be stopped by this
maneuver. If it is ineffective (i.e., the seizure activity is
spreading or generalizing), however, intravenous propofol
(30-50 mg) should be administered and repeated as
necessary. The patient must be closely watched for
seizure recurrence or airway compromise. Most
intraoperative seizures are resolved without adverse
consequences, although apnea and cardiac arrest can
occur. Airway instrumentation is normally not needed.
When needed, it is often the result of excessive propofol
For an obstructed airway emergency, a rapid differential
diagnosis is needed to identify the cause. In parallel, one
should alert the surgeon, call for help, stop all infusions,
and mask-ventilate the patient with 100% inspired oxygen
with appropriate jaw thrust, perhaps facilitated by an oral
or nasal airway. In anticipation of such a life-threatening
event, there should always be an LMA, syringe, and
lubricant at hand. Some also like to have an ETT and video
laryngoscope within reach. An LMA should be placed if
mask ventilation fails or if the situation otherwise mandates
it. It can be difficult to position an LMA in a semi-lateral
patient whose head is slightly turned and secured in a
pinned head frame. The tongue can be pulled out using a
4 9 400 gauze or Magill forceps to facilitate LMA
placement, if needed. The patient can be intubated using
a video laryngoscope with the anesthesiologist standing in
front of the patient, although it is better done with the
assistance of an additional skilled anesthesiologist. Lastly,
if the ventilation crisis is due to remifentanil-induced apnea
or chest rigidity, one should attempt mask-ventilation while
at the same time stopping the remifentanil infusion. These
actions may be sufficient to resolve the crisis. Low-dose
succinylcholine (*0.5 mg kg-1) should be used promptly
if the crisis (chest rigidity) is not quickly aborted by other
measures, although there are no clinical trial data to
support this practice.
Goals during the asleep-to-awake Smooth and rapid return of the baseline mental status; avoid somnolence, confusion, agitation, and delirium
Airway management during the
GA vs MAC for the pre-awake
Visit and establish good rapport with the patient; explain to patient the relevant details of the perioperative
care; answer questions
Pre-awake phase [[ awake phase [[ post-awake phase
GA with LMA vs MAC with or without nasopharyngeal airway. Some authors prefer light to moderate MAC
with the patient drowsy but readily arousable
LMA (GA) vs nasopharyngeal airway (MAC) vs no airway instrumentation (MAC)
Differ in airway management, ventilation mode (mechanical vs spontaneous), and physiological disturbances;
may also differ in the impact on anti-tumour immunity, oncological outcomes, and patient’s survival
The goal is to have an engaging, cooperative, pain-free, comfortable patient. No or minimal sedation (e.g.,
remifentanil), ice chips/water to wet the lip and mouth, face scratch for itching, position adjustment of
shoulders/hips/legs, supplemental local anesthetic injection for pain (and possibly intravenous
acetaminophen), comfortable room temperature, air blanket for comfort, euvolemia, empathy, and
Have a video laryngoscope in room; have an LMA (different sizes) with lubricant and an endotracheal tube
with a stylet handy; have propofol and succinylcholine in syringe. If airway emergency, call for helper, stop
infusions, mask-ventilate (with an oropharyngeal or nasopharyngeal airway), try to place an LMA if no
improvement with mask ventilation (may need to pull the tongue out to facilitate the placement), try to
intubate the patient using video laryngoscope by standing in front of the patient if LMA fails; surgeon to lift
drapes out of the way while preserving sterility
Irrigate ice-cold saline solution onto the cortex, small propofol bolus (30-50 mg) if needed; think ABC
(airway, breathing, circulation); supportive if patient recovers; convert to GA if necessary; show empathy
and comfort the patient if neurological complications (e.g. worsening weakness or language, paralysis) with
the understanding that some deficits are recoverable
LMA is normally not replaced even if used during the pre-awake phase. Sedation often suffices, as patients
are often fatigued
Large variation in practice. Decision to admit to ICU, floor, or discharge home on the same day should be
based on patient’s condition and institutional experience. Early discharge with a well-established backup
plan is the current trend
Outcome-oriented studies comparing GA vs MAC for the pre-awake phase; prevention and treatment of
emergence confusion/delirium; impacts of different airway management; impact of anesthetic agents on
brain tumor outcomes
GA = general anesthesia; ICU = intensive care unit; LMA = laryngeal mask airway; MAC = monitored anesthesia care
Sedation is normally restarted, and the case can usually be
finished without an LMA even if it was used during the
pre-awake phase. The patient typically requires lower rates
of sedative infusions during the post-awake phase than
during the pre-awake phase. This may be due to fatigue
from the awake phase, release of the psychological
pressure after learning of successful lesion removal, and
the lower level of painful stimuli during skull closure
compared with that at skull opening. The goal of sedation
is to keep the patient drowsy but without airway
The rapid recovery after AC has revolutionized the
subsequent care of these patients. A recent systematic
review concluded that AC is associated with a much shorter
hospital stay (four days) than craniotomy under GA (nine
days) based on seven comparative studies (P value
unreported).11 On average (median), patients are
discharged home on day 3 (range days 2-20) after awake
brain tumour resection by the program at University of
California San Francisco.6 The program at Toronto Western
Hospital also reported a median three-day hospital stay
(range, days 0-47),90 with some patients discharged home on
the same day of surgery.91,92 Most institutions admit the
patient to a neuro-intensive care unit for close overnight
observation after AC, although others see this as overly
conservative.90,91 The postoperative visit provides an
important opportunity for anesthesia providers to learn
from the patient about the parts of the procedure that he or she
found most difficult. The short-term outcomes associated
with AC, in contrast to those associated with conventional
craniotomy under GA, can also be better appreciated with
this early postoperative visit.
Quality research and evidence can improve patient outcomes
via standardization of clinical practice and the resolution of
controversial topics. Obvious controversies in the anesthetic
care for AC include optimal airway management, the choice
of GA vs MAC, deep sedation vs light to moderate sedation,
and the choice of anesthetic/sedative agents during the
preawake stage. The outcomes of most concern to patients (e.g.,
tumour recurrence, survival) should be used as the end points
of research targeting these controversies.93 For example,
emergence delirium (assessed shortly after anesthesia) has a
high prevalence and has been linked to postoperative
delirium (assessed on and after postoperative day 1).94-96
Clinically, emergence delirium (hypoactive or hyperactive)
following the asleep-to-awake transition during AC does
occur, especially when the pre-awake phase is managed
under GA or deep sedation. The patients who experience
persistent delirium stay in the intensive care unit and hospital
longer,97,98 have prolonged mechanical ventilation,98 incur
more health care cost,99 and are at increased risk for
dementia, institutionalization, and death after hospital
discharge.100-103 One of the potential modifiable risk
factors for perioperative delirium is the anesthesia
‘‘depth,’’ characterized by electroencephalography
monitoring (i.e., deeper anesthesia is associated with a
higher incidence of delirium).104-109 However, whether
keeping the patient under light to moderate sedation,
instead of deep sedation or GA, during the pre-awake
phase of AC is effective in preventing or reducing the
incidence of emergence confusion/delirium remains to be
determined. Whether the use of processed EEG anesthesia
‘‘depth’’ monitoring is beneficial during the anesthetic care
for AC is another intriguing research topic. Finally, the effect
of anesthetic agents on brain tumour progression or
recurrence and patient survival should be prioritized in
The improvement in anesthetic care has made a major
contribution to the increasing popularity of AC. Thirteen
aspects of the anesthetic management of patients
undergoing AC have been discussed and summarized
(Table 2). The majority of the technical ‘pearls’ are
preference/opinion-based because of the lack of
comparative evidence. Research is not always feasible
when taking into account the scientific merits, priorities,
and costs. Therefore, expert experience/opinion will
continue to play an important role in clinical practice and
the successful facilitation of AC.
Acknowledgements Support was provided solely from institutional
and/or departmental sources. The authors thank Dr. Weiliang Zhang
(Department of Anesthesiology, Affiliated Hospital of Shandong
Traditional Chinese Medicine University, Jinan, Shandong Province,
China) for his invaluable assistance with preparation of the figures.
Conflict of interest None declared.
Editorial responsibility This submission was handled by Dr.
Hilary P. Grocott, Editor-in-Chief, Canadian Journal of Anesthesia.
Author contributions Lingzhong Meng, David L. McDonagh,
Mitchel S. Berger, and Adrian W. Gelb contributed substantially to
the conception and design of this review article. Lingzhong Meng and
David L. McDonagh drafted the article. Lingzhong Meng, David L.
McDonagh, Mitchel S. Berger, and Adrian W. Gelb critically revised
Financial support and sponsorship
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