Anesthesia for awake neurosurgery

Federico Bilotta and Giovanni Rosa

Department of Anesthesiology, Critical Care and Pain
Medicine, Sapienza University of Rome, Rome, Italy
Correspondence to Federico Bilotta, MD, PhD, via
Acherusio 16, Rome 00199, Italy
Tel: +39 06 339 33 708 22; e-mail: bilotta@tiscali.it
Current Opinion in Anaesthesiology 2009,
22:560565
Purpose of review
In this review we focus on recent findings in the anesthetic management of patients
undergoing craniotomy while awake, and propose a structured approach to the clinical
practice of anesthesia for awake neurosurgery.
Recent findings
The increasing use of functional neurosurgery and recent evidence favoring resection of
tumor involving eloquent cortex has expanded the indications for awake craniotomy, a
procedure needing a fully cooperative patient and expert intraoperative anesthetic
management. Despite the shorter hospital stay, the more recently published studies
have highlighted perioperative anesthetic complications and have proposed ways to
improve anesthesia techniques for awake procedures in adults and children.
Summary
Although anesthesia for awake craniotomy is usually a well tolerated procedure it
requires an extensive knowledge of the principles underlying neuroanesthesia and of
specific technical strategies including local anesthesia for scalp blockade, advanced
airway management, dedicated sedation protocols, and skillful management of
hemodynamics.

Keywords
awake craniotomy, neuroanesthesia, scalp blockade

Curr Opin Anaesthesiol 22:560565

2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
0952-7907

are used to provide anesthesia for awake neurosurgery,

Introduction
Anesthesia for awake craniotomy is a unique clinical
setting that requires the anesthesiologist to provide
changing states of sedation and analgesia, to ensure
optimal patient comfort without interfering with electro-
physiologic monitoring and patient cooperation, but
also to manipulate cerebral and systemic hemodynamic
while guaranteeing adequate ventilation and airways
safety [1,2]. Awake craniotomy is the preferred approach
for functional neurosurgery (including deep-brain stimu-
lation for the treatment of Parkinsons disease, and, more
recently, for the treatment of various other conditions
including obesity and severe obsessive compulsive dis-
orders) [35]. It is also indicated for epilepsy surgery
[610], and for neurosurgical procedures requiring intra-
operative monitoring of speech and motor functions to
localize the area of surgical interest (including resection
or biopsy of brain tumors in eloquent areas) since it allows
wider tumor excision and lower perioperative morbidity
[1114].
In these patients the anesthesiologist has to accomplish
various tasks including local anesthesia, airway manage-
ment, sedation and analgesia, and management of
systemic and cerebral hemodynamics. Many techniques
0952-7907 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
on the basis of different institutional protocols or patients
tailored needs. These techniques range from local
anesthesia, with or without conscious sedation, to general
anesthesia with the asleep-awake-asleep sequence, with
or without airway instrumentation [15,16].
The review aims to present the most recent evidence
from the clinical literature but also to propose a struc-
tured approach to the practice of anesthesia for
awake neurosurgery.
Local anesthesia
Adequate local anesthesia, aimed to block the sensory
branches of the trigeminal nerve, is essential to provide
anesthesia for awake neurosurgery. Scalp block with
local anesthetic provides reversible regional loss of sen-
sation, reduces pain perception and global energy expen-
diture [17]. In some cases, especially in Parkinsonian
patients undergoing microelectrode implantation for
deep-brain stimulation, local anesthesia is the only
possible anesthetic approach since infusion of sedatives
may abolish brain impulses during microelectrode record-
ings in subcortical areas. These areas are highly sensitive
to GABAergic anesthetics drugs that even at small
DOI:10.1097/ACO.0b013e3283302339

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Table 1 Special needs and anesthetic adjuncts in the different surgical procedures
Surgical procedure Special needs
Deep-brain stimulation Lack of interference
with recording
Excision of epileptic focus Lack of interference with
electro-corticography and
functional testing
Tumor surgery next to eloquent areas or Ability to perform
motor cortex and map motor cortex functional testing
LMA, laryngeal mask airway.
doses can critically reduce the ability to identify the sites
to be excised [18,19] [Table 1].
A recent review on the management of anesthesia in
awake craniotomy by Piccioni and Fanzio [20], and a case
series of 42 patients by Sinha et al. [2] that reports
the incidence of perioperative complications in these
patients, describe the technique for selectively blocking
the sensory branches of the trigeminal nerve. This
approach is based on infiltration of six nerves: the aur-
iculotemporal nerve, zygomaticotemporal nerve, supra-
orbital nerve, supratrochlear nerve, greater occipital
nerve, and lesser occipital nerve. Both investigators also
recommend infiltrating the head-holder pin site and the
surgical skin incision line [2,20].
In a prospective, randomized, placebo-controlled study,
Geze et al. [21] compared the effects on hemodynamic
and stress responses of local infiltration for scalp block or
selective block of the sensory trigeminal nerve branches,
in patients undergoing general anesthesia for craniot-
omy. In this study, the investigators compared local
anesthesia infiltrated at the scalp pin-insertion site (with
5 ml of 0.5% bupivacaine) added to infiltration of the
surgical skin incision line (with 20 ml of 0.5% bupiva-
caine) with a selective block of the sensory trigeminal
nerve branches (with 25 ml of 0.5% bupivacaine at each
site). The investigators concluded that the selective
trigeminal nerve block is more effective than local infil-
tration for scalp block in controlling hemodynamic
responses and in preventing the increased stress hor-
Table 2 Anesthesia for awake neurosurgery (operative flow chart)
Premedication
Local anesthesia
Selective scalp block or cranial circular scalp block
Infiltration of skin incision line and head-holder pin site
Intraoperative sedationanalgesia
If LMA is used (asleep-awake-asleep technique)
Postoperative analgesia
Hemodynamic management
when hypertensive
when hypotensive
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Anesthesia for awake neurosurgery Bilotta and Rosa 561
Technique Anesthetic adjuncts
Local anesthesia Avoid GABAergic drugs
Dexmedetomidine infusion
Asleep-awake-asleep Dexmedetomidine infusion
sequence with LMA
Asleep-awake-asleep Local anesthesia or similar to above
sequence
mone response to skull-pin fixation for craniotomies.
Also in children undergoing general anesthesia for
craniotomy, scalp nerve block with levobupivacaine
0.25% (2 mg/kg) with epinephrine 2.5 mcg/ml seems a
well tolerated and effective procedure that prevents and
reduces postoperative pain [22]. These observations
might extend to patients receiving local anesthesia for
awake neurosurgery.
Although the timing, site, and optimal drug selection for
scalp block remain open to question, our experience and
published reports suggest that in most patients, a circular
scalp block combined with infiltration of head-holder pin
sites and surgical incision line with either bupivacaine,
levobupivacaine, or ropivacaine provides adequate local
anesthesia with minimal or no risks for systemic toxicity
[2,23,24] [Table 2].
Airway management
A prerequisite for safe management of anesthesia for
awake neurosurgery is expertise in advanced airway
management. In managing the airways of awake non-
intubated patients it is essential to ensure adequate
oxygen supply and carbon dioxide removal (to avoid the
dangerous effects of carbon dioxide on cerebral blood
flow and extracellular pH), but also to prevent aspiration.
In a retrospective review of perioperative complications
in 258 procedures involving 250 patients undergoing
awake neurosurgery for deep-brain stimulation, Khatib
Midazolam 0.0150.03 mg/kg
Fentanyl 12 mg/kg
Bupivacaine 0.5%, or ropivacaine 0.5%, or levobupivacaine 0.5%:
up to a total of 2040 ml
Bupivacaine 0.5%, or ropivacaine 0.5%, or levobupivacaine 0.5%:
up to a total of 1015 ml
Propofol 13 mg/kg/h; fentanyl 13 mg/kg/h, or remifentanil
0.010.25 mg/kg/h; dexmedetomidine 0.30.7 mg/kg/h
Sevoflurane 0.51% MAC
Paracetamol 1 g twice daily and/or morphine 0.10.3 mg/kg/die
Esmolol (bolus infusion), metoprolol, labetalol, diltiazem or clonidine
Ephedrine bolus 0.30.5 mg/kg
 562 Neuroanaesthesia
et al. [19] showed that although airway complications
are rare, they described respiratory arrest or severe airway
obstruction in up to 1.6% of the cases, and intraoperative
cough, moaning, or sneezing in up to 1.2%. The data from
the case series by Sinha et al. [2] confirm the need to
devote adequate attention to severe adverse respiratory
complications. In their series, hypercarbia with end-tidal
CO2 greater than 50 mmHg complicated 9.5% of the
cases, respiratory depression with respiratory rate less
than 8 breaths/min complicated 7.1% of the cases, and
desaturation with SpO2 less than 95% was present in
4.8%. In a study describing two cases of intraoperative
respiratory complications in patients undergoing asleep-
awake-asleep techniques [16], in one case hypercarbia
developed with EtCO2 greater than 48 mmHg during
craniotomy while the patient was spontaneously breath-
ing through the laryngeal mask airway (LMA) and was
successfully treated by gentle assisted manual venti-
lation. In the other case, slight hypercarbia with EtCO2
of 45 mmHg complicated by mild bulging of the brain
developed during the awake phase of surgery and
required prompt repositioning of the LMA. Severe oxy-
gen desaturation during which SpO2 values drop to 70%
can lead to myocardial ischemia [25]. Airway instrumen-
tation might therefore be needed at any surgical stage, as
well as on an emergency basis. Hence assessing airways
preoperatively and keeping supraglottic airway devices
and flexible fiber optic bronchoscope readily available is
important. As highlighted by Conte et al. [26], to reduce
further the risk of perioperative complications, patients
must be carefully selected and detailed clinical com-
munication should be maintained between the anesthe-
siological and surgical teams.
Additional evidence underlining the importance of ade-
quate PaCO2 removal during awake neurosurgery comes
from a clinical study by Khu and Ng [27] who showed
that patients undergoing tumor removal with awake
anesthesia require a larger craniotomy than those receiv-
ing general anesthesia, owing to increased brain swelling
and compression on the craniotomy edges possibly partly
related to higher PaCO2 levels. Equally important,
patients undergoing awake craniotomy cannot receive
hyperventilation to control cerebral edema when a con-
duit to mechanical ventilation in the form of an endo-
tracheal tube is absent.
In patients undergoing awake craniotomy the various
airway devices currently available range from simple
nasopharyngeal cannulas to a modified tracheal tube
allowing topical delivery of local anesthesia and reintu-
bation over a fiberoptic bronchoscope [15,28]. A major
technical advance that has met wide consensus is the use
of an LMA for awake craniotomy in patients breathing
spontaneously. This approach has the advantage of being
accomplished without a laryngoscope and head exten-
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sion, and is associated with a lower incidence of coughing
and gagging [15,29,30]. Although various techniques can
be used for LMA positioning during anesthesia for
awake neurosurgery, proper positioning (even when
the approach requires lateral or semi-sitting position) is
extremely important so that the anesthsiologist can easily
maneuver the airway and the patient feels comfortable
during awake surgery [20,31]. In a case report Huncke
et al. [32] described the successful use of an LMA along
with continuous positive-pressure ventilation in a mor-
bidly obese patients with obstructive sleep apnea under-
going awake craniotomy to remove a brain lesion adjacent
to the language areas. Although nasopharyngeal cannulas
have been recommended to improve intraoperative
ventilatory exchange [20,33] they carry a risk of intranasal
bleeding, may be difficult to position, and might interfere
with the surgical field [15].
Our experience suggests that in most spontaneously
breathing patients, giving 50% FiO2 via a facial mask
guarantees adequate oxygenation and does not suppress
ventilatory drive. The real-time EtCO2 concentration,
sampled in the upper airways, provides useful infor-
mation on ventilatory mechanics, and can prompt gentle
facial mask ventilatory support if hypercarbia develops.
Inadequate airway safety or ventilation a complication
that may arise during seizures or intractable cough
should be treated with appropriate sedation and LMA
positioning or fiberoptic-guided endotracheal intubation.
Sedation and analgesia
In delivering anesthesia for awake neurosurgery, a
dedicated sedationanalgesia protocol is of paramount
importance because oversedation may lead to an unco-
operative patient and cause respiratory depression to
develop, whereas undersedation makes the patient
uncomfortable, agitated, and leads to unstable hemody-
namics (especially arterial hypertension and tachycardia).
In a prospective study designed to assess prevalent
emotions and feelings in patients undergoing awake cra-
niotomy for brain tumor resection, Palese et al. [34] report
that at least half of the patients describe craniotomy as the
worst experience during the whole operation, hence the
importance of adequate sedation during this early pro-
cedural stage. In a prospective observational, two-armed
study Hol et al. [35] showed that after adequate intra-
operative sedationanalgesia awake craniotomy can be
physically and emotionally less stressful than general
anesthesia. As drugs for intraoperative sedation and
analgesia, consensus confirms the established role of propo-
folfentanyl [16,2], propofolremifentanil [16,35], and
dexmedetomidine. Dexmedetomidine with or without
concurrent useof propofol providessedation that resembles
natural sleep, without respiratory depression [18,28].

Although some evidence suggests titrating propofol infu-
sion with intraoperative bispectral index monitoring
[2,16], in patients undergoing awake neurosurgery an
equally important concern is to set up an adequate
strategy also for postoperative pain control [36,37]. Remi-
fentanil is a well tolerated opioid and provides good
intraoperative pain control but sometimes induces post-
operative complications including hyperalgesia and
hypertension or tachycardia [38,39].
To provide a dedicated intraoperative and postoperative
sedationanalgesia protocol is also important because
awake craniotomy, owing to its low complication rate, is
broadening the use of brain surgery on a day-case basis, thus
considerably reducing costs and utilization of resources by
minimizing intensive care time and total hospital stay
without compromising patient care [35,40,41].
In our experience, the preoperative infusion of fentanyl
13 mg/kg in addition to intraoperative use of paraceta-
mol, a drug that also provides some transitory analgesia,
and propofol infusion titrated to the changing levels of
sedation needed, will in most patients provide adequate
analgesia and sedation. In North America, most anesthe-
siologists prefer to provide adjunctive intraoperative
analgesia with remifentanil infusion (Table 2).
Hemodynamic management
One of the most challenging tasks of anesthesia for
awake neurosurgery is optimization of operating con-
ditions by manipulating systemic and cerebral hemo-
dynamics. In most cases, relative hypotension or normo-
tension is indicated to reduce bleeding and brain
swelling during brain exposure, whereas normal blood
pressure is essential for surgical hemostasis; and ade-
quate hemodynamic manipulation is often required to
prevent arterial hypertension, thus minimizing the risk
of postoperative intracranial hemorrhage.
In their clinical study, Khatib et al. [19] showed an
overall complication rate of 11.6% in patients undergoing
awake neurosurgery for deep-brain stimulation. The
most frequent complications were neurologic (3.6%)
and among these, intracranial hemorrhage had the high-
est incidence, up to 2.8% of the patients. Hence preven-
tion and aggressive treatment of arterial hypertension is
important. The data from the case series by Sinha et al. [2]
confirm and extend the importance of careful manage-
ment of systemic hemodynamics. They reported that
arterial hypertension with systolic blood pressure rising
by more than 30% from baseline values complicated 19%
of the procedures, tachycardia with heart rate of more
than 140 beats/min complicated 7.1% of the cases and
bradycardia with a heart rate of less than 50 beats/min
complicated 4.8% of the cases.
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Anesthesia for awake neurosurgery Bilotta and Rosa 563
In a clinical study of patients who underwent craniotomy
with propofolremifentanil-based general anesthesia our
group [39] found that postoperative infusion of esmolol
effectively blunts the hemodynamic changes (namely
arterial hypertension and tachycardia) that frequently
arise when remifentanil is discontinued. These benefits
might extend also to patients undergoing remifentanil-
based anesthesia for awake neurosurgery. Severe arterial
hypertension and tachycardia need to be prevented or
promptly treated because both events can lead to myo-
cardial ischemia [25].
In our experience various antihypertensive medications
including beta blockers [2,25,39], calcium-channel
antagonists [42], and a-adrenergic receptor agonists [16]
can be safely and effectively used to manipulate arterial
blood pressure, whereas nitrates should be avoided
because they can induce major changes in cerebral blood
volume leading to brain swelling (Table 2).
Clinical research
Apart from the need for controlled trials aimed to improve
the delivery of anesthesia for awake neurosurgery, this
setting offers a unique scenario for clinical research in
neurosciences and in neuroanesthesia. In a prospective
study, Pennings et al. [43] investigated brain tissue oxy-
gen pressure in awake patients undergoing deep-brain
stimulation. This study originally reported that the mean
intraoperative partial brain tissue oxygen pressure is
markedly lower in awake patients than in patients under-
going craniotomy for neurovascular disease or brain
tumors under general anesthesia (23 vs. 3348 mmHg).
It also underlines that the long adaptation time renders
partial brain tissue oxygen pressure values unreliable in
detecting ischemia early after electrode insertion and
limits its usefulness for intraoperative monitoring.
In a prospective study Hol et al. [35] tested an innovative
approach for measuring perioperative stress by quanti-
tatively assaying plasma amino acid concentrations in
patients undergoing craniotomy under awake or general
anesthesia. Their findings suggest that patients under-
going awake neurosurgery had fewer changes in plasma
amino acid profile and that this quantitative approach holds
promise for monitoring postoperative pain and recovery.
Seeking to improve methods for monitoring postopera-
tive pain and recovery in patients undergoing anesthesia
for awake neurosurgery, Sinha et al. [2] describe the use of
bispectral index monitoring. Their results confirm and
extend previous evidence in patients receiving general
anesthesia showing that this monitoring technique
reduces consumption of anesthetics but unless a cost-
effectiveness analysis proves otherwise it might increase
total costs owing to the expensive electrodes required.
 564 Neuroanaesthesia
Conclusion
Anesthesia for awake craniotomy is a well tolerated
procedure that requires an extensive knowledge of the
principle underlying neuroanesthesia and of specific
strategies including local anesthesia for scalp blockade,
advanced airway management, dedicated sedation
analgesia protocols, and skillful management of hemo-
dynamics. Among the various needs are intraoperative
and postoperative analgesia (induced with both local
anesthesia and systemic sedationanalgesia), adequate
ventilation, systemic and cerebral hemodynamic man-
agement, with no interference from electrophysiologic
monitoring while mapping the area of surgical interest,
and full patient cooperation. These possibly conflicting
targets sometimes makes the clinical practice of
anesthesia for awake craniotomy a challenging and
demanding task.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
 of special interest
 of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 687).
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